Iodoethane → (S)-1-(2-benzyl-4-(1-cyclobutyl-3-ethyl-1H-indazol-6-yl)piperazin-1-yl)-2-(1-ethyl-1H-pyrazol-4-yl)ethanone

HRID 1423206Notes

Reaction equation

[CH2:1]([C@H:8]1[CH2:13][N:12]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([CH2:27][CH3:28])=[N:19][N:20]3[CH:23]3[CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=2)[CH2:11][CH2:10][N:9]1[C:29](=[O:36])[CH2:30][C:31]1[CH:32]=[N:33][NH:34][CH:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:39](I)[CH3:40]>CN(C=O)C.CCOC(C)=O>[CH2:1]([C@H:8]1[CH2:13][N:12]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([CH2:27][CH3:28])=[N:19][N:20]3[CH:23]3[CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=2)[CH2:11][CH2:10][N:9]1[C:29](=[O:36])[CH2:30][C:31]1[CH:32]=[N:33][N:34]([CH2:39][CH3:40])[CH:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of (S)-1-(2-benzyl-4-(1-cyclobutyl-3-ethyl-1H-indazol-6-yl)piperazin-1-yl)-2-(1H-pyrazol-4-yl)ethanone (101 mg, 0.21 mmol) in DMF (1 mL) was treated with sodium hydride (10 mg, 0.25 mmol) as a 60% dispersion in mineral oil. Once bubbling subsided, ethyl iodide (18 μL, 0.23 mmol) was added and the mixture was heated to 60° C. for 24 h. The reaction mixture was diluted with EtOAc (30 mL) and washed with water (5 mL) followed by brine (5 mL). The organic layer was dried over Na2SO4, filtered, and evaporated. The crude residue was purified by silica gel chromatography eluting with a 0-10% MeOH in CH2Cl2 gradient to afford product as a colorless solid (48 mg, 44%). LC/MS 4.03 min, [M+1]+ 511.

Workup

customOnce bubbling
washwashed with water (5 mL)
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
customevaporated
customThe crude residue was purified by silica gel chromatography
washeluting with a 0-10% MeOH in CH2Cl2 gradient

Sources & evidence

ORD record: ord-76a551103c0240d3948dfdbd0cf70931
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927546B2

Reaction notes

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