8-Amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

General procedure: Thionyl chloride (1.6g, 13mmol) was added to a mixture of 13a (597mg, 2.0mmol), DCE (10mL), and 3 drops of DMF under cooling in an ice-water bath, and the solution was stirred for 2h at room temperature. The reaction solution was concentrated under reduced pressure. DCE (20mL), 6-amino-1, 3-dihydro-2H-indol-2-one (269mg, 1.82mmol), and triethylamine (726mg, 7.17mmol) were added to the residue, and the mixture was stirred at room temperature for 12h. Water was added to the reaction mixture and the aqueous phase was extracted with CHCl3. The combined organic phase was washed with water, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3/MeOH/28% aqueous NH3) to obtain a light yellow solid, which was dissolved in EtOH/EtOAc and a 4M hydrogen chloride solution in EtOAc was added. The solvent was removed by evaporation and the residue was triturated with EtOH to give 20 as a pale pink powder (273mg, 32% yield).A solution of 8-bromo- 1 -(3 , 4-dichlorobenzyl)-3 , 7-dimethyl- 1H-purine-2, 6(3H, 7H)-dione (165 mg, 0.40 mmol), 8-amino-4, 5-dihydro-1H-benzo[b]azepin-2(31])-one(106 mg, 0.60 mmol), Pd(OAc)2 (18 mg, 0.08 mmol), Xantphos (92 mg, 0.16 mmol) andCs2CO3 (391 mg, 1.2 mmol) in DMF (2 mL) was stirred at 120 C for 1 h. The mixture waspurified by Prep-HPLC using Method D (30-70% ACN). 'H NIVIR (400 MHz, DMSO-d6)9.66 (s, 1H), 9.22 (s, 1H), 7.63-7.52 (m, 2H), 7.44 (d, J= 2.0 Hz, 1H), 7.37 (dd, J= 8.2, 2.1Hz, 1H), 7.29 (dd, J= 8.4, 1.9 Hz, 1H), 7.17 (d, J= 8.3 Hz, 1H), 5.02 (s, 2H), 3.77 (s, 3H), 3.44 (s, 3H), 2.63 (t, J 6.9 Hz, 2H), 2.24- 2.13 (m, 2H), 2.12-1.99 (m, 2H); ESI: m/z 513.0(M+H)+General procedure: To a solu&et of 6, S-dlbrornci- [l, 2, 4J So[1, 5-&yrathE (0.21 0.72] rtuuol, Ark Pliant) and 5- anth4th-1Herr]-an-Z3hJrE (0.12 g, 0.7'2 numi, Astatecl irue-PrOH (S ruL) was added DEA (0377 niL, 2.16 rtutvl). The nixthrr was heated to reflux for abat 24 k The resu1iir so]u&nwas cooled to it and filtered to give 8-((b-[L24kcc[LJvrath8- yVn&-45thkv&c?-JH-bo(bJ'zn'in-2(3Scv2e (0.15 g, 55percent) as a brtwn solid: 'H NMR (DM5 0-dEl) oe 9.62 (s, 1H), S.69 (s, lH 5S9 (s, 1H), 7.61-7.67 (ii, , 2H), 723(d, frS.4 H; 1H), 2.65 Qt, 1=6.4 H; 2H 2.07-2. 15 (m, 3H 1.23 (rr 1H).Example No. 218 Preparation of 3- (7- ( (2-oxo-2 , 3 , 4 , 5- tetrahydro-lH- benzo [b] azepin-8-yl) amino) -IH-pyrazolo [4 , 3 -d] pyrimidin- 5- yl) benzoic acid3- (7-chloro-2- (4-methoxybenzyl) -2H-pyrazolo [4 , 3-d] pyrimidin-5- yl) benzoic acid methyl ester (0.16 mmol) and 8-amino-4, 5- dihydro-lH-benzo [b] azepin-2 (3H) -one (0.3 mmol 2 eq. , ) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HC1 in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was disolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions . The mixture was irradiated in a micrawave reactor for 10 min at 120C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.exact mass: 414.1673 g/molHPLC-MS: analytical method Lrt: 4.04 min - found mass: 415 (m/z+H)Example No. 217Preparation of methyl 3- (7- ( (2-oxo-2 , 3 , 4 , 5-tetrahydro-lH- benzo [b] azepin-8-yl) amino) -IH-pyrazolo [4, 3-d] pyrimidin- 5- yl) benzoate methyl 3- (7-chloro-2- (4-methoxybenzyl) -2H-pyrazolo [4, 3- d] pyrimidin- 5 -yl) benzoate (0.16 mmol) and 8 -amino-4 , 5 -dihydro- lH-benzo [b] azepin-2 (3H) -one (0.3 mmol 2 eq. , ) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HC1 in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was concentrated and purified by semi- preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 428.1868 g/molHPLC-MS: analytical method Lrt: 4.65 min - found mass: 429 (m/z+H)Example No. 164Preparation of 8- ( (5- (4-methoxyphenyl) -lH-pyrazolo [4 , 3- d] pyrimidin-7-yl) amino) -4 , 5-dihydro-lH-benzo [b] azepin-2 (3H) - one7-chloro-2- (4-methoxybenzyl) -5- (4-methoxyphenyl) -2H- pyrazolo [4 , 3 -d] yrimidine (0.16 mmol) and 8 -amino-4 , 5 -dihydro- lH-benzo [b] azepin-2 (3H) -one (0.3 mmol 2 eq., ) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HCl in dioxane (4 , 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was concentrated and purified by semi- preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 400.1928 g/molHPLC-MS: analytical method Art: 2.33 min - found mass: 401 (m/z+H)Example No.8: 8-(4-(Cyclopropylamino)furo[3, 2-i/]pyrimidin-2-ylamino)-4, 5-dihydro-l/ - benzo[6]azepin-2(3/7)-oneA flask was charged with 2-chloro-A^-cyclopropylfuro[3, 2-i/]pyrimidin-4-amine (0.50 g, 2.385 mmol, Example No.3, Step C), 8-amino-4, 5-dihydro-l//-benzo[ft]azepin-2(3//)-one (0.420 g, 2.385 mmol, Astatech), K2C03 (0.989 g, 7.16 mmol) and i-BuOH (9 mL). The flask was purged with N2 for 10 min. Pd2dba3 (0.153 g, 0.167 mmol) and X-Phos (0.159 g, 0.334 mmol) was added. The flask was again purged with N2 for 5 min and the mixture was heated to about 85 C for about 18 h. The mixture was cooled to rt. The mixture was partitioned between DCM (200 mL) and water (200 mL) and the aqueous layer was extracted with DCM (3 x 100 mL). The combined organic layers were concentrated under reduced pressure. The resulting residue was suspended in EtOAc (200 mL) and trituated. The suspension was filtered and the solid was collected and washed with EtOAc (50 mL). The solid was suspended in a mixture solvents of DCM (100 mL) and MeOH (10 mL), filtered to give a gray solid, which was purified by preparative reverse phase HPLC (Table 2, method v). The fractions were collected then most of the MeCN was removed under reduced pressure, the resulting suspension was filtered and the solid was collected to give 8-(4-(cyclopropylamino)mro[3, 2-J]pyrimidin-2-ylamino)-4, 5-dihydro-l//-benzo[ft]azepin-2(3//)- one (0.338 g, 40%): LC/MS (Table 2, Method c) Rt = 1.80 min; MS m/z: 350 (M+H)+. Syk IC50 = A

Molecular Weight:176.21
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:176.094963011
Monoisotopic Mass:176.094963011
Topological Polar Surface Area:55.1
Heavy Atom Count:13
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes