1,2,3,4-TETRAHYDRO-6-QUINOLINECARBOXYLICACID

l-Acetyl-1, 2, 3, 4-tetrahydro-quinoline-6-carbonitrile (50 mmol) was refluxed in HC1 (8M) (150 mL) for 18h. The mixture was cooled and pH adjusted to approx. 3 with NaOH. The product precipitated and was removed by filtration, washed with water and dried. Yield: 61percent 1H NMR (D6-DMSO) : 1.79 (m, 2H); 2.68 (m, 2H) ; 3.23 (m, 2H); 5.45 (br, 1H) ; 6. 48 (d, 1H) ; 7.45-7. 50 (2H).General procedure: Step 32-methyl-A mixture of l, 2, 3, 4-tetrahydroquinoline-6-carboxylic acid (500 mg, 2.82 mmol), (R)-N- (1024) (pyrrolidin-3-yl)quinazolin-2-amine hydrochloride (848 mg, 3.38 mmol), HATU (1.28 g, 3.38 mmol) and DIEA (1.09 mL, 8.46 mmol) in DMF (50 mL) was stirred at rt overnight. The mixture was diluted with water (20 mL) and extracted with DCM (20 mL* 3). The combined organic layer was washed with brine (20 mL), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by column chromatography (PE:EA = 1 : 1) to afford (R)-(3-(quinazolin-2- ylamino)pyrrolidin-l-yl)(l, 2, 3, 4-tetrahydroquinolin-6-yl)methanone (230 mg, 23%) as light yellow solid. [M+H] Calc'd for C22H23N5O, 374.4; Found, 374.4To a solution of 1 , 2, 3, 4-tetrahydroquinoline-6-carboxylic acid (5g, 28.2 mmol), sodium bicarbonate (21.3 g, 254 mmol) in water (25 ml) and Dioxane (25 ml) was added benzyl chloroformate (5.29 g, 31 mmol) and the reaction was stirred at RT overnight. (0409) The solution was acidified to pH 3 with the addition of 1 N HCI and extracted with DCM (3 x 25 ml.) and the combined organic layer was dried over Na2S04 and concentrated under reduced pressure to give (7.15 g, 81 %) crude product (6S-06). The material was used in the next step without further purification. LCMS: (APCI) m/e 312.0 (M+1).

Molecular Weight:177.20
XLogP3:1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:177.078978594
Monoisotopic Mass:177.078978594
Topological Polar Surface Area:49.3
Heavy Atom Count:13
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes