2-Aminothiazole → (S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(3H-pyrrol-2-yl)-1H-benzo[d]imidazole-4-carboxamide

HRID 85135Notes

Reaction equation

HRID 85135 reaction equation
[F:1][CH:2]([F:30])[C:3]1[CH:8]=[C:7]([O:9][CH2:10][C@H:11]2[CH2:15][O:14][C:13]([CH3:17])([CH3:16])[O:12]2)[CH:6]=[CH:5][C:4]=1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][CH:25]=[C:26]([C:27](O)=[O:28])[C:20]=2[N:19]=1.S1C=CN=C1N.CN(C(ON1N=[N:52][C:47]2[CH:48]=[CH:49][CH:50]=[N:51]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:30][CH:2]([F:1])[C:3]1[CH:8]=[C:7]([O:9][CH2:10][C@H:11]2[CH2:15][O:14][C:13]([CH3:16])([CH3:17])[O:12]2)[CH:6]=[CH:5][C:4]=1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][CH:25]=[C:26]([C:27]([NH:52][C:47]3[CH2:48][CH:49]=[CH:50][N:51]=3)=[O:28])[C:20]=2[N:19]=1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67202420(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole-4-carboxylic acid

Product 1

HCID 86653796(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(3H-pyrrol-2-yl)-1H-benzo[d]imidazole-4-carboxamideYield 66.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole-4-carboxylic acid (67; 100 mg, 0.239 mmol) was taken up in 10 ml of DMF along with 2-aminothiazole (4; 28.7 mg, 0.289 mmol), HATU (181.7 mg, 0.478 mmol) and DIEA (61.8 mg, 0.289 mmol). The resulting reaction mixture was stirred at room temperature for 12 h and diluted with water. The precipitated solids were collected by filtration and dried. Purification by chromatography (EtOAc/Hexane=2:1) afforded (S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide 68 (77 mg, 65%). MS (ESI) calcd for C24H22F2N4O4S: 500.13; found: 501 [M+H].

Workup

  1. customThe resulting reaction mixture
  2. filtrationThe precipitated solids were collected by filtration
  3. customdried
  4. customPurification by chromatography (EtOAc/Hexane=2:1)

Sources & evidence

ORD record
ord-dd269dcac0504a0595b29b92d5b69e85
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

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