1-Methyl-5-(tri-n-butylstannyl)imidazole → HCID 86709782, compound

HRID 1529395Notes

Reaction equation

HRID 1529395 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.[CH3:39][N:40]1[C:44]([Sn](CCCC)(CCCC)CCCC)=[CH:43][N:42]=[CH:41]1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:39][N:40]1[C:44]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[N:6]=[C:5]3[C:17]2[N:22]=[C:21]([O:23][C@H:24]3[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:25]43[CH2:27][CH2:26]4)[CH:20]=[N:19][CH:18]=2)=[CH:43][N:42]=[CH:41]1

Participants

5

Reactant 2

HCID 109156511-Methyl-5-(tri-n-butylstannyl)imidazoleHCID 67959732HCID 67959732, compound

Product 1

HCID 86709782HCID 86709782, compoundYield 183.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution 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 (147 mg, 0.251 mmol), 1-methyl-5-(tributylstannyl)-1H-imidazole (Synthonix, Inc., Wake Forest, N.C.; 0.099 mL, 0.327 mmol), and Pd(PPh3)4 (14.53 mg, 0.013 mmol) in DMF (2.0 mL) was heated under argon at 100° C. for 2.5 h. The reaction was cooled to RT, concentrated onto silica gel, and chromatographically purified (ISCO, 12 g silica gel column, 0-10% MeOH/DCM, 20 min, 254 nm) to provide crude (4R)-tert-butyl 4-(6-(5-(1-methyl-1H-imidazol-5-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (270.3 mg; contaminated with PPh3 and DMF) as a yellow-orange foam: MS (ESI, pos. ion) m/z: 586.2 (M+1). This material was used without further purification in the subsequent step.

Workup

  1. concentrationconcentrated onto silica gel
  2. customchromatographically purified (ISCO, 12 g silica gel column, 0-10% MeOH/DCM, 20 min, 254 nm)

Sources & evidence

ORD record
ord-12a368125da143f1954d062714fdcbd8
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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