Water → HCID 86762243, compound

HRID 338151Notes

Reaction equation

[F:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[Cl-].[S:19]1[C:23]([C@:24]23[CH2:32][NH2+:31][CH2:30][C@H:29]2[CH2:28][S:27][C:26]([NH:33][C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[N:25]3)=[CH:22][CH:21]=[N:20]1.O>CN1CCCC1=O>[F:1][C:2]1[CH:3]=[N:4][C:5]([N:31]2[CH2:30][C@@H:29]3[C@@:24]([C:23]4[S:19][N:20]=[CH:21][CH:22]=4)([N:25]=[C:26]([NH:33][C:34](=[O:41])[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[S:27][CH2:28]3)[CH2:32]2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

5-Fluoro-2-chloropyrimidine (58 mL, 608.3 mol), and diisopropylethylamine (227 mL 1.30 mol, 227.3 mL) is added to N-[(4aR,7aR)-7a-isothiazol-5-yl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-6-ium-2-yl]benzamide chloride (174.2 g, 434.5 mol), in N-methylpyrrolidone (1.4 L) at 22° C. and stirred. The reaction is heated at 100° C. for 4 hours and then cooled to room temperature. The crude mixture is added to water (14 L) and then stirred 1 hour. A white solid is collected by filtration and dried under vacuum to constant weight. The crude product is purified by silica gel chromatography, eluting with ethyl acetate: methylene chloride (3/1) to give the title compound (139 g, 72%). ES/MS (m/e): 441.0 (M+H).

Workup

temperaturecooled to room temperature
stirringstirred 1 hour
filtrationA white solid is collected by filtration
customdried under vacuum to constant weight
customThe crude product is purified by silica gel chromatography
washeluting with ethyl acetate

Sources & evidence

ORD record: ord-7cf0a84b26004866a62365eb3be1ca3c
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889856B2

Reaction notes

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