Water → 6-(2-Amino-4-pyrimidinyl)-4-(methyloxy)-1H-indazol-3-amine

HRID 2367204Notes

Reaction equation

[C:1]([C:3]1[C:8](F)=[CH:7][C:6]([C:10]2[CH:15]=[C:14](C)[N:13]=[C:12]([NH:17]C(=O)C)[N:11]=2)=[CH:5][C:4]=1F)#[N:2].[H-].[Na+].O.[NH2:25][NH2:26].O.CN([CH:31]=[O:32])C>CCO>[NH2:17][C:12]1[N:11]=[C:10]([C:6]2[CH:5]=[C:4]3[C:3]([C:1]([NH2:2])=[N:25][NH:26]3)=[C:8]([O:32][CH3:31])[CH:7]=2)[CH:15]=[CH:14][N:13]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of N-[4-(4-cyano-3,5-difluorophenyl)-6-methyl-2-pyrimidinyl]acetamide in DMF (3 mL) was added sodium hydride (1.5 eq.). To the basic solution was added dropwise a solution of the appropriate alcohol (1 eq.) and sodium hydride (1 eq.) in DMF (3 mL). The vial that contained the alkoxide solution was rinsed with more DMF (1 mL). When the reaction was judged complete (HPLC, ˜1 hour), the reaction mixture was poured onto saturated aqueous ammonium chloride. After standing for ˜10-15 minutes, the precipitate formed was collected by vacuum filtration. To the resulting solid in EtOH was added hydrazine monohydrate (50 eq.), and the reaction mixture was stirred overnight at 90° C. The reaction was poured onto EtOAc and water. The organic phase was separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were concentrated. Work-up from here varies according to the compound.

Workup

washwas rinsed with more DMF (1 mL)
custom(HPLC, ˜1 hour)
additionthe reaction mixture was poured onto saturated aqueous ammonium chloride
customthe precipitate formed
filtrationwas collected by vacuum filtration
customThe organic phase was separated
extractionthe aqueous layer was further extracted with EtOAc
concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record: ord-e157c618ac9b4a7db583d4ec1e9827f3
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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