Diisopropylethylamine → methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate

HRID 655742Notes

Reaction equation

HRID 655742 reaction equation
Cl[C:2]1[S:3][C:4]([C:19]([O:21][CH3:22])=[O:20])=[C:5]([C:7]2[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH:10]=[CH:9][N:8]=2)[N:6]=1.C(N(CC)C(C)C)(C)C.[Cl:32][C:33]1[C:37]([Cl:38])=[C:36]([CH3:39])[NH:35][C:34]=1[C:40]([NH:42][C@@H:43]1[CH2:48][CH2:47][NH:46][CH2:45][C@@H:44]1[O:49][CH3:50])=[O:41]>CN1CCCC1=O.O>[Cl:32][C:33]1[C:37]([Cl:38])=[C:36]([CH3:39])[NH:35][C:34]=1[C:40]([NH:42][C@@H:43]1[CH2:48][CH2:47][N:46]([C:2]2[S:3][C:4]([C:19]([O:21][CH3:22])=[O:20])=[C:5]([C:7]3[N:12]=[C:11]([N:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[CH:10]=[CH:9][N:8]=3)[N:6]=2)[CH2:45][C@@H:44]1[O:49][CH3:50])=[O:41]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 59402524Methyl 2-chloro-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate2×HCID 667077643,4-dichloro-N-[(3S,4R)-3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide

Product 1

HCID 59402451methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylateYield 71.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of methyl 2-chloro-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate (Intermediate 67, 30 mg, 0.08 mmol) in N-methylpyrrolidinone (0.5 mL), N,N-diisopropyl ethylamine (23 mg, 0.18 mmol) and 3,4-dichloro-N-[(3S,4R)-3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide (WO2006087543, 27 mg, 0.09 mol) were added at room temperature. The above reaction mixture was heated at 90° C. for 3 h. The reaction mixture was cooled to room temperature, diluted with water (5 mL) and stirred for 1 h. The solid obtained was collected by filtration and dried to obtain methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate 35 mg (66%).

Workup

  1. customThe above reaction mixture
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe solid obtained
  4. filtrationwas collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-c0117a36dae8441aa0acabf56e4e9fc7
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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