2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine → 4-amino-2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]pyrimidin-5-ol

HRID 1776396Notes

Reaction equation

[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([O:21]C)=[CH:16][N:15]=2)=[N:6]1>CN1CCCC1=O>[NH2:20][C:18]1[C:17]([OH:21])=[CH:16][N:15]=[C:14]([C:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[N:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[F:1])[N:6]=2)[N:19]=1

Participants

Conditions

Temperature: 140 °C

Procedure

558 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine (1-4-2, 1.60 mmol, 1 eq.) was suspended in 10 ml of 1-methyl-2-pyrrolidon. 623 mg of sodium sulfidosodium (7.99 mmol, 5 eq.) were added and stirred for an hour at 140° C. The reaction mixture was extracted with half-saturated aq. ammonium chloride-solution and ethyl acetate. The aqueous layer was reextracted twice by ethyl acetate. The aqueous layer gave a precipitate, which was filtered off and first purified by flash chromatography (hexane/dichloro methane/methanol), followed by a HPLC purification. This provided 23.4 mg (0.07 mmol, 4.37%) of the analytically pure target compound.

Workup

extractionThe reaction mixture was extracted with half-saturated aq. ammonium chloride-solution and ethyl acetate
customThe aqueous layer gave a precipitate, which
filtrationwas filtered off
customfirst purified by flash chromatography (hexane/dichloro methane/methanol)
customfollowed by a HPLC purification

Sources & evidence

ORD record: ord-942f0ba90f324882acafd3531ed59040
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265763B2

Reaction notes

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