Water → HCID 66613759, compound

HRID 473173Notes

Reaction equation

[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]([F:37])([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=1)[C:9]1[N:18]=[C:17]([NH:19][C:20]2[CH:24]=[C:23]([CH3:25])[NH:22][N:21]=2)[C:16]2[C:11](=[CH:12][C:13]([C:26](OC)=[O:27])=[CH:14][CH:15]=2)[N:10]=1.O.[OH-].[Na+]>C1COCC1>[F:37][C:8]([F:7])([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=1)[C:9]1[N:18]=[C:17]([NH:19][C:20]2[CH:24]=[C:23]([CH3:25])[NH:22][N:21]=2)[C:16]2[C:11](=[CH:12][C:13]([CH2:26][OH:27])=[CH:14][CH:15]=2)[N:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of lithium aluminum hydride (LAH, 3 equiv) in THF at 0° C. is slowly added a suspension of methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(5-methyl-1H-pyrazol-3-ylamino)quinazoline-7-carboxylate (1 equiv) in THF. The mixture is stirred at 0° C. for 0.5 h and then at rt for 4 h. To the stirring mixture at 0° C. are added successively in dropwise fashion water (1 mL per g of LAH), 15% NaOH (1 mL per g of LAH), and water (3 mL per gram of LAH) and the mixture is stirred at rt overnight. The mixture is filtered through Celite washing with 20% MeOH/DCM (500 mL), and the filtrate is concentrated under reduced pressure. The residue is purified by reverse phase HPLC to afford (2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-7-yl)methanol.

Workup

additionis slowly added
waitat rt for 4 h
stirringthe mixture is stirred at rt overnight
filtrationThe mixture is filtered through Celite
washwashing with 20% MeOH/DCM (500 mL)
concentrationthe filtrate is concentrated under reduced pressure
customThe residue is purified by reverse phase HPLC

Sources & evidence

ORD record: ord-7a0b7e6e006e47009c2f19b85546427b
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633207B2

Reaction notes

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