Potassium Carbonate → methyl 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1-cyclopentyl-1H-indazole-4-carboxylate

HRID 1501714Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[C:20]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.[Cu]I.O>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][N:30]([C:2]2[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]3[CH:6]=[N:7][N:8]([CH:11]4[CH2:15][CH2:14][CH2:13][CH2:12]4)[C:9]=3[CH:10]=2)[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate (5 g, 15.527 mmol) in DMSO (25 mL), 1-Boc piperazine (4.3 g, 23.3 mmol), K2CO3 (4.28 g, 31.05 mmol), CuI (0.295 g, 1.55 mmol) and L-proline (0.357 g, 3.1 mmol) were added in given order and resulting reaction mixture heated to 100° C. for 48 h. On completion, the reaction mixture was poured into water and extracted with DCM. The combined organic layers were washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure to obtain crude residue which was purified by column chromatography over silica gel affording methyl 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1-cyclopentyl-1H-indazole-4-carboxylate (2 g, 30%).

Workup

customresulting
customreaction mixture
extractionextracted with DCM
washThe combined organic layers were washed with water
dry with materialdried over sodium sulfate
customThe solvent was removed under reduced pressure
customto obtain crude residue which
customwas purified by column chromatography over silica gel

Sources & evidence

ORD record: ord-6c62a0fbe4e043fda838580cfa02d13a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206157B2

Reaction notes

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