Sodium hydride → HCID 71612144, compound

HRID 1484695Notes

Reaction equation

[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[C:15]([F:16])=[CH:14][C:13]([CH:17]4[CH2:19][CH2:18]4)=[CH:12][C:11]=3[F:20])[N:7]=[C:6]([C:21]3[N:26]=[C:25]([NH2:27])[C:24]([O:28][CH3:29])=[CH:23][N:22]=3)[C:5]=2[CH3:30])[CH2:3][CH2:2]1.Cl.F[C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1.[H-].[Na+]>CN(C=O)C>[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[C:15]([F:16])=[CH:14][C:13]([CH:17]4[CH2:19][CH2:18]4)=[CH:12][C:11]=3[F:20])[N:7]=[C:6]([C:21]3[N:26]=[C:25]([NH:27][C:33]4[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=4)[C:24]([O:28][CH3:29])=[CH:23][N:22]=3)[C:5]=2[CH3:30])[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 90 °C

Procedure

16.5 mg of 2-[5-cyclopropyl-1-(4-cyclopropyl-2,6-difluorobenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxypyrimidin-4-amine 1-17-3 (0.040 mmol, 1.0 eq.) and 16.1 mg 4-Fluoropyridine hydrochlorid (0.120 mmol, 3.0 eq.) were suspended in 0.19 mL dry DMF under a nitrogen atmosphere. 19.2 mg of sodium hydride (60% purity) were added and stirred at 90° C. for 2 h. Then the mixture was partitioned between half water and ethyl acetate. The aqueous layer was washed with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography to obtain 5.7 mg (0.01 mmol, 20%) of the analytical pure target compound.

Workup

customThen the mixture was partitioned between half water and ethyl acetate
washThe aqueous layer was washed with ethyl acetate twice
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography

Sources & evidence

ORD record: ord-4f52896ef68d49658c49d427a6c09305
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422268B2

Reaction notes

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