Ammonium Chloride → 2-Chloro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one

HRID 1429716Notes

Reaction equation

[CH2:1]([N:4]1[C:12](=[O:13])[C:11]2[NH:10][C:9]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=4)[CH:18]=3)=[N:8][C:7]=2[NH:6][C:5]1=O)[CH2:2][CH3:3].[NH4+].[Cl-:32]>O=P(Cl)(Cl)Cl>[Cl:32][C:5]1[N:4]([CH2:1][CH2:2][CH3:3])[C:12](=[O:13])[C:11]2[NH:10][C:9]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=4)[CH:18]=3)=[N:8][C:7]=2[N:6]=1

Participants

Conditions

Temperature: 122.5 °C

Procedure

A mixture of 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-3,7-dihydro-purine-2,6-dione (7.2 g, 0.017 mol), NH4Cl (4.54 g, 0.085 mol) and POCl3 (220 ml) were heated at 120-125° C. for 72 h. Reaction mixture was cooled to 20-25° C. It was then concentrated under vacuum and quenched with cold water slowly and solid material was separated. It was filtered off and washed with water. The solid material was dried under vacuum. The crude product was purified by column chromatography using silica gel (230-400 mesh) and 0.5 to 4% methanol in chloroform as an eluent to obtain 2-Chloro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (4.2 g, 58%) as a pale yellow solid.

Workup

customReaction mixture
temperaturewas cooled to 20-25° C
concentrationIt was then concentrated under vacuum
customquenched with cold water slowly
customsolid material was separated
filtrationIt was filtered off
washwashed with water
customThe solid material was dried under vacuum
customThe crude product was purified by column chromatography

Sources & evidence

ORD record: ord-512425df17044f17ba92af3131cf45fa
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940751B2

Reaction notes

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