Formaldehyde → HCID 53345179, compound

HRID 1404299Notes

Reaction equation

C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][CH:22]=[C:23]([C:25]4[C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[N:28]=[C:27]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=5[F:41])[CH:26]=4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C=O>C(O)=O>[F:41][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=1[C:27]1[CH:26]=[C:25]([C:23]2[CH:22]=[N:21][CH:20]=[C:19]([C:17]3[CH:16]=[N:15][N:14]([CH:11]4[CH2:12][CH2:13][N:8]([CH3:6])[CH2:9][CH2:10]4)[CH:18]=3)[CH:24]=2)[C:34]2[C:29](=[N:30][CH:31]=[CH:32][CH:33]=2)[N:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 286 mg (0.52 mmol) 4-(4-{5-[2-(2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (synthesis see example 8) in 1.7 ml formic acid was treated with 124 mg (1.56 mmol) 35% aqueous formaldehyde solution and heated to 80° C. The reaction mixture was stirred at this temperature for two hours. The volume of the reaction mixture was reduced under vacuum and the residue was partitioned between 2 N NaOH and dichloromethane. The organic phase was dried over sodium sulphate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 2-(2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine as colourless solid; HPLC/MS: 1.37 min, [M+H] 465.

Workup

customthe residue was partitioned between 2 N NaOH and dichloromethane
dry with materialThe organic phase was dried over sodium sulphate
customevaporated
customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record: ord-d717710388f140468ffacaebaf3e4f1e
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912216B2

Reaction notes

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