2,4-di-chloropyrimidine 5-carboxylic acid amide

Synthesis of 5-Carboxyamide-2, 4-DichloropyrimidineConcentrated ammonium hydroxide solution in HTo a solution of 2, 4-dichloropyrimidine-5- carbonyl chloride (6.2 g, 29.3 mmol) in 1, 4-dioxane (50 mL) was added ammonia (1.0 g, 58.3 mmol) in 1, 4-dioxane (50 mL) dropwise at 0 °C, and the resulting solution was stirred for 12 h at ambient temperature. The mixture was diluted with ethyl acetate (50 mL), and washed with water (2 x 80 mL) and brine (2 x 80 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound as a white solid (4.5 g, 80percent). MS (ESI): m/z = 191.8 [M + H]5.1.32 The solution containing Compound E-i from Step 2.1 was directly engaged in Step 2.2 at -15 C or -5/0 C. Cyclopropylamine was added in the solution with or without the addition of a base (DIPEA) to obtain Compound A-1. In one batch, 2.0 equivalents of cyclopropylamine were added to the solution. After 2 hrs of reaction, 0.08 % of Compound E-i was present. fter completion of Step 2.2, the organic phase (MeTHF) was washed with water, which was followed by a solvent swap from MeTHF to NMP to obtain a solution of Compound A-i inNMP.The 2, 4 - dichloro pyrimidine -5 - carboxamide (100 mg, 0 . 52 mmol) dissolved in tetrahydrofuran (4 ml) in, respectively adding (2 - fluoro -4 - nitrophenyl) methylamine hydrochloride (108 mg, 0 . 52 mmol) and diisopropyl serotonin reuptake (202 mg, 1 . 57 mmol), 25 C reaction 2 hours. Add saturated salt water (40 ml), stirring 15 minutes later, filtering solid, washing the filter cake with petroleum ether, to get the yellow solid 120 mg, yield 71%.The 2, 4 - dichloro pyrimidine -5 - carboxamide (200 mg, 1 . 04 mmol) dissolved in tetrahydrofuran (5 ml) in, respectively adding 4 - (2 - aminoethyl) piperidine -1 - formic acid tert-butyl (238 mg, 1 . 04 mmol) and diisopropyl serotonin reuptake (404 mg, 3 . 13 mmol), 25 C reaction 2 hours. Add saturated salt water (50 ml), stirring 15 minutes after the filtering, the filter cake washing petroleum ether, to obtain white solid 270 mg, yield 68%The 2, 4 - dichloro pyrimidine -5 - carboxamide (100 mg, 0 . 52 mmol) dissolved in tetrahydrofuran (4 ml) in, respectively adding 4 - (aminomethyl) piperidine -1 - formic acid tert-butyl ester (112 mg, 0 . 52 mmol) and diisopropyl serotonin reuptake (202 mg, 1 . 57 mmol), 25 C reaction 2 hours. Add saturated salt water (40 ml), stirring 15 minutes after the filtering, the filter cake washing petroleum ether, to obtain white solid 150 mg, yield 79%.The 2, 4 - dichloro pyrimidine -5 - carboxamide (100 mg, 0 . 52 mmol) dissolved in tetrahydrofuran (4 ml) in, respectively adding alanine methyl ester hydrochloride (73 mg, 0 . 52 mmol) and diisopropyl serotonin reuptake (202 mg, 1 . 56 mmol), 25 C reaction 2 hours. Add saturated salt water (40 ml), stirring 15 minutes after the filtering, the filter cake washing petroleum ether, to obtain white solid 90 mg, yield 67%.The 2, 4 - dichloro pyrimidine -5 - carboxamide (100 mg, 0 . 52 mmol) dissolved in tetrahydrofuran (4 ml) in, respectively adding 5 - amino -1 - pentanol (54 mg, 0 . 52 mmol) and diisopropyl serotonin reuptake (202 mg, 1 . 56 mmol), 25 C reaction 2 hours. Add saturated salt water (40 ml), stirring 15 minutes later, filtering solid, washing the filter cake with petroleum ether, to obtain white solid 80 mg, yield 59%.The 2, 4 - dichloro pyrimidine -5 - formamide (210 mg, 1 . 09 mmol) dissolved in tetrahydrofuran (8 ml) in, respectively adding (2, 6 - difluorophenyl) methylamine (156 mg, 1 . 09 mmol) and diisopropyl serotonin reuptake (423 mg, 3 . 27 mmol), 25 C reaction 2 hours. Add saturated salt water (80 ml), stirring 15 minutes after the filtering, the filter cake washing petroleum ether, to obtain white solid 285 mg, yield 87%.

Molecular Weight:192.00
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:190.9653171
Monoisotopic Mass:190.9653171
Topological Polar Surface Area:68.9
Heavy Atom Count:11
Complexity:166
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes