Hydrochloric Acid → HCID 118117630, compound

HRID 1485575Notes

Reaction equation

HRID 1485575 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]=[CH:13][N:14]=[C:15]([NH:18][CH:19]4[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)[C:16]=3[N:17]=2)=[CH:4][C:3]=1[NH:32][S:33]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=1[F:43])(=[O:35])=[O:34].Cl>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:3]([NH:32][S:33]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=2[F:43])(=[O:34])=[O:35])=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]=[CH:13][N:14]=[C:15]([NH:18][CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[C:16]=3[N:17]=2)=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66558476HCID 66558476, compound

Product 1

HCID 118117630HCID 118117630, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(6-(6-chloro-5-(2,4-difluorophenylsulfonamido)pyridin-3-yl)pyrido[3,2-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (12.0 g, 19.0 mmol; prepared as in Example 1, Step B) in DCM (300 mL) was added HCl (4 M in 1,4-dioxane) at 0° C., and the reaction mixture was stirred for 4 h at room temperature. The solvent was removed by evaporation, and the obtained crude N-(2-chloro-5-(4-(piperidin-4-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide HCl salt was used for the next step without further purification. TEA (26.4 mL, 190 mmol) was added to a suspension of above obtained HCl salt in DCM (300 mL) at 0° C. The mixture was stirred for 1 h at room temperature and isopropyl carbonochloridate (19.0 mL, 19.0 mmol) was added to the reaction mixture at 0° C. The reaction mixture was stirred for 2 h at room temperature. DCM and water were poured into the residue, and the separated aqueous layer was extracted with DCM, the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc:MeOH=20:1) to give isopropyl 4-(6-(6-chloro-5-(2,4-difluorophenylsulfonamido)pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (9.87 g, 84%) as a pale yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.21 (6H, d, J=6.4 Hz), 1.62-1.78 (2H, m), 1.85-1.95 (2H, m), 2.82-3.08 (2H, m), 4.02-4.17 (2H, m), 4.40-4.54 (1H, m), 4.77-4.83 (1H, m), 7.22 (1H, dt, J=2.4, 8.8 Hz), 7.53-7.61 (1H, m), 7.74-7.83 (1H, m), 8.21 (1H, d, J=8.8 Hz), 8.42 (1H, d, J=10.8 Hz), 8.46 (1H, d, J=8.8 Hz), 8.54 (1H, s), 8.66 (1H, d, J=2.4 Hz), 9.39 (1H, d, J=2.4 Hz). NH peak was not observed. m/z=618.2 [M+1]+.

Workup

  1. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-596bbf2b1ac0460c90268cd5087f4350
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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