1-Methylimidazole → Methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate

HRID 1410013Notes

Reaction equation

HRID 1410013 reaction equation
Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[OH:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][C:37]=1[C:38]([O:40][CH3:41])=[O:39])[C:32](O)=[O:33].CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[CH3:27][O:26][C:20]1[CH:19]=[C:18]([NH:17][C:10]2[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=[C:8]([N:5]3[CH2:6][CH2:7][CH:3]([NH:2][C:32]([C:31]4[CH:35]=[CH:36][C:37]([C:38]([O:40][CH3:41])=[O:39])=[C:29]([OH:28])[CH:30]=4)=[O:33])[CH2:4]3)[N:9]=2)[CH:23]=[CH:22][C:21]=1[O:24][CH3:25]

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 670501783-Hydroxy-4-(methoxycarbonyl)benzoic acidHCID 683792715-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

Product 1

HCID 68379322Methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoateYield 45.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (164 mg, 0.4 mmol), 3-hydroxy-4-(methoxycarbonyl)benzoic acid (78 mg, 0.4 mmol), EDCI (153 mg, 0.8 mmol) and N-methylimidazole (100 mg, 1.2 mmol) in 5 mL of DCM was stirred at room temperature for 16 hours. The mixture was washed with water (4 mL), The organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography (silica gel, 100% DCM to DCM:MeOH=50:1) to give methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate (100 mg, yield 45%). LC-MS: 551 [M+H]+, tR=1.61 min.

Workup

  1. washThe mixture was washed with water (4 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified by column chromatography (silica gel, 100% DCM to DCM:MeOH=50:1)

Sources & evidence

ORD record
ord-bfe88ea28a324d249477650f3ebb9b8c
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

Loading…