Diisopropylethylamine → N-[(4aR,7aS)-6-(5-Fluoro-4-isopropyl-pyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 470263Notes

Reaction equation

HRID 470263 reaction equation
Cl.[C:2]1([C@:8]23[CH2:16][NH:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:9]3)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:36]1[N:41]=[C:40]([CH:42]([CH3:44])[CH3:43])[C:39]([F:45])=[CH:38][N:37]=1>O1CCOCC1.O.C(=O)(O)[O-].[Na+]>[F:45][C:39]1[C:40]([CH:42]([CH3:44])[CH3:43])=[N:41][C:36]([N:15]2[CH2:14][C@@H:13]3[C@@:8]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)([N:9]=[C:10]([NH:17][C:18](=[O:25])[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[S:11][CH2:12]3)[CH2:16]2)=[N:37][CH:38]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 583334102-Chloro-5-fluoro-4-isopropyl-pyrimidineHCID 86762232N-[(4aR,7aS)-7a-phenyl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide hydrochloride

Product 1

HCID 86762231N-[(4aR,7aS)-6-(5-Fluoro-4-isopropyl-pyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamideYield 3,090.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of N-[(4aR,7aS)-7a-phenyl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide hydrochloride (285 mg, 7.62 μmol), diisopropylethylamine (798 μL, 4.57 mmol) and 2-chloro-5-fluoro-4-isopropyl-pyrimidine (0.798 g, 4.57 mmol) in 1,4-dioxane (15 mL) is heated to 100° C. for eight hours under nitrogen. The reaction mixture is cooled and diluted with water and aqueous saturated sodium bicarbonate. The mixture is extracted with ethyl acetate (3×). The combined organic layers are dried over sodium sulfate and the solvent is removed under vacuum. The crude product is purified over silica gel eluting with a 5% to 100% ethyl acetate in hexanes gradient, to give the title compound (112 mg, 31%). ES/MS (m/e): 476 (M+H).

Workup

  1. temperatureThe reaction mixture is cooled
  2. extractionThe mixture is extracted with ethyl acetate (3×)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. customthe solvent is removed under vacuum
  5. customThe crude product is purified over silica gel eluting with a 5% to 100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-c5e74d04f9ff464ab3ffeff1899b7f95
Source dataset
uspto-grants-2014_01
Patent number
US08629270B2

Reaction notes

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