Water → methyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate

HRID 655746Notes

Reaction equation

HRID 655746 reaction equation
Cl[C:2]1[S:3][C:4]([C:13]([O:15][CH3:16])=[O:14])=[C:5]([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][N:8]=2)[N:6]=1.[Cl:17][C:18]1[CH:19]=[C:20]([C:24]([NH:26][C@H:27]2[CH2:32][CH2:31][NH:30][CH2:29][C@H:28]2[O:33][CH2:34][CH2:35][CH3:36])=[O:25])[NH:21][C:22]=1[CH3:23].CCN(C(C)C)C(C)C.O>CN1CCCC1=O>[Cl:17][C:18]1[CH:19]=[C:20]([C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][N:30]([C:2]3[S:3][C:4]([C:13]([O:15][CH3:16])=[O:14])=[C:5]([C:7]4[N:11]([CH3:12])[N:10]=[CH:9][N:8]=4)[N:6]=3)[CH2:29][C@@H:28]2[O:33][CH2:34][CH2:35][CH3:36])=[O:25])[NH:21][C:22]=1[CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 59208415Methyl 2-chloro-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate2×HCID 667074514-chloro-5-methyl-N-[(3R,4S)-3-propoxypiperidin-4-yl]-1H-pyrrole-2-carboxamide2×

Product 1

HCID 59402555methyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylateYield 57.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 2-chloro-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate (Intermediate 2, 68 mg, 0.267 mmol) was added to a solution of 4-chloro-5-methyl-N-[(3R,4S)-3-propoxypiperidin-4-yl]-1H-pyrrole-2-carboxamide (Intermediate 74, 80 mg, 0.267 mmol) and DIPEA (0.04 mL, 0.8025 mmol) in N-methyl 2-pyrrolidinone (1.0 mL) and the resulting reaction mixture was stirred overnight at 80° C. The reaction mixture was cooled to room temperature and poured into water (30 mL). The solid that formed was collected by filtration, washed well with diethyl ether (30 mL) and dried to afford methyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate 80 mg (57.1%) as solid.

Workup

  1. customthe resulting reaction mixture
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe solid that formed
  4. filtrationwas collected by filtration
  5. washwashed well with diethyl ether (30 mL)
  6. customdried

Sources & evidence

ORD record
ord-fcb2294027ca4029b8d2923cde232fd9
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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