Potassium Carbonate → (S)-5-(4-hydroxy-4-methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((5-methyl-1-(pyrimidin-2-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)dione

HRID 131636Notes

Reaction equation

[OH:1][C@:2]1([CH3:35])[CH2:6][O:5][N:4]([C:7]([C:9]2[C:17]3[C:16](=[O:18])[N:15]([CH3:19])[C:14](=[O:20])[N:13]([CH:21]([CH3:23])[CH3:22])[C:12]=3[S:11][C:10]=2[CH2:24][C:25]2[C:26]([C:31]([F:34])([F:33])[F:32])=[N:27][NH:28][C:29]=2[CH3:30])=[O:8])[CH2:3]1.Br[C:37]1[N:42]=[CH:41][CH:40]=[CH:39][N:38]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu]I>[CH3:35][C@@:2]1([OH:1])[CH2:6][O:5][N:4]([C:7]([C:9]2[C:17]3[C:16](=[O:18])[N:15]([CH3:19])[C:14](=[O:20])[N:13]([CH:21]([CH3:22])[CH3:23])[C:12]=3[S:11][C:10]=2[CH2:24][C:25]2[C:26]([C:31]([F:32])([F:33])[F:34])=[N:27][N:28]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[C:29]=2[CH3:30])=[O:8])[CH2:3]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of the product of example 10 part b) (279 mg), 2-bromopyrimidine (300 mg), copper(I) iodide (95 mg), trans-cyclohexanediamine (55 mg) and potassium carbonate (300 mg) in dioxane (2 ml) was heated at 100° C. for 16 hours under nitrogen. The reaction mixture was concentrated to dryness and purified by silica chromatography eluting with an ethyl acetate to 10% methanol/ethyl acetate gradient, followed by RPHPLC to give the title compound as a white solid (105 mg).

Workup

concentrationThe reaction mixture was concentrated to dryness
custompurified by silica chromatography
washeluting with an ethyl acetate to 10% methanol/ethyl acetate gradient

Sources & evidence

ORD record: ord-e476f1203fc547f59b9bf6281bff1113
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07384951B2

Reaction notes

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