Methanol → HCID 67959712, compound

HRID 1529406Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:17]1[N:22]=[C:21]([O:23][C@H:24]2[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:25]32[CH2:27][CH2:26]3)[CH:20]=[N:19][CH:18]=1.[C:39]([O-:42])(=[O:41])C.[K+].[CH3:44]O>>[C:35]([O:34][C:32]([N:30]1[CH2:29][CH2:28][C:25]2([CH2:26][CH2:27]2)[C@@H:24]([O:23][C:21]2[N:22]=[C:17]([C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([C:39]([O:42][CH3:44])=[O:41])[CH:3]=4)[N:7]([CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[N:6]=3)[CH:18]=[N:19][CH:20]=2)[CH2:31]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

Reactant 3

HCID 887Methanol

HCID 517044Potassium Acetate

HCID 67959732HCID 67959732, compound

Product 1

HCID 67959712HCID 67959712, compoundYield 83%

Procedure

A mixture of (4R)-tert-butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (150 mg, 0.257 mmol), PdCl2dppf (20.96 mg, 0.026 mmol), and potassium acetate (76 mg, 0.770 mmol) in MeOH (2566 μL) was placed in a Symyx/Argonaut reactor for 16 h at 90° C. under CO (70 psi) when clean conversion was observed via 1 cms. The crude was purified via automated flash chromatography (silica gel) with 100% hexanes to 20% EtOAc/hexanes to give methyl 3-(6-((R)-6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octan-4-yloxy)pyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (120 mg, 0.213 mmol, 83% yield) as a colorless oil. MS (ESI, pos. ion) m/z: 564.2 (M+1).

Workup

customThe crude was purified

Sources & evidence

ORD record: ord-050a6f115d7442349bb3c7898b31075d
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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