Water → N-[(4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 338148Notes

Reaction equation

HRID 338148 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C@:6]12[CH2:14][NH:13][CH2:12][C@H:11]1[CH2:10][S:9][C:8]([NH:15][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[N:7]2.CN(C)C(N(C)C)=N.[F:32][C:33]1[CH:34]=[N:35][C:36](Cl)=[N:37][CH:38]=1.O>CS(C)=O>[F:32][C:33]1[CH:34]=[N:35][C:36]([N:13]2[CH2:12][C@@H:11]3[C@@:6]([C:2]4[S:1][CH:5]=[CH:4][CH:3]=4)([N:7]=[C:8]([NH:15][C:16](=[O:23])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[S:9][CH2:10]3)[CH2:14]2)=[N:37][CH:38]=1

Participants

6

Reactant 4

HCID 962WaterHCID 664601,1,3,3-TetramethylguanidineHCID 5834662-Chloro-5-fluoropyrimidineHCID 86762223HCID 86762223, compound

Product 1

HCID 86762240N-[(4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamideYield 71%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of N-[(4aR,7aR)-7a-(2-thienyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (7.7 g, 22.4) and N,N,N′,N′-tetramethylguanidine (3.39 mL, 26.9 mmol) in dimethyl sulfoxide (61 mL) is treated with 5-fluoro-2-chloropyrimidine (2.25 mL, 23.54 mmol) and the resulting solution is heated at 50° C. for 4 hours. The solution is cooled to room temperature and added to water (500 mL). The crude product is purified over silica gel using a 5 to 50% gradient of ethyl acetate/hexanes to give the title compound (7 g, 71%). ES/MS (m/e): 440 (M+H).

Workup

  1. temperatureThe solution is cooled to room temperature
  2. customThe crude product is purified over silica gel using a 5 to 50% gradient of ethyl acetate/hexanes

Sources & evidence

ORD record
ord-eeeb5f98653e4e6ca2edbe51ba08b48d
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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