Potassium tert-butoxide → 1-({(5S,7S)-3-[5-(1,1-dimethylethyl)-3-isoxazolyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl}methyl)-1H-benzimidazole-6-carbonitrile

HRID 715519Notes

Reaction equation

[CH3:1][C@:2]1([CH2:10][N:11]2[C:15]3[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)CCC[C@:4]2(OC2)[CH2:3]1.[CH3:22][C:23]([C:26]1[O:30][N:29]=[C:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH:27]=1)([CH3:25])[CH3:24].CC(C)([O-])C.[K+]>CN1C(=O)CCC1>[CH3:25][C:23]([C:26]1[O:30][N:29]=[C:28]([N:31]2[CH2:35][C@@:34]3([CH2:37][CH2:4][CH2:3][C@@:2]([CH2:10][N:11]4[C:15]5[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=5[N:13]=[CH:12]4)([CH3:1])[CH2:36]3)[O:33][C:32]2=[O:38])[CH:27]=1)([CH3:22])[CH3:24]

Participants

Conditions

Temperature: 125 °C

Procedure

1-{[(3S,5S)-5-methyl-1-oxaspiro[2.5]oct-5-yl]methyl}-1H-benzimidazole-6-carbonitrile (150 mg, 0.533 mmol), 1,1-dimethylethyl [5-(1,1-dimethylethyl)-3-isoxazolyl]carbamate (320 mg, 1.333 mmol) and potassium tert-butoxide (78 mg, 0.693 mmol) were added to a 10 mL microwave vial while nitrogen purging. Then, NMP (3 mL) was added and the vial was capped and heated to 125° C. for 16 h. The reaction was filtered and purified to give 42 mg (13.3%) of 1-({(5S,7S)-3-[5-(1,1-dimethylethyl)-3-isoxazolyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl}methyl)-1H-benzimidazole-6-carbonitrile. 1H NMR (400 MHz, MeOH-d4) δ 8.43 (br. s., 1H), 8.19 (s, 1H), 7.82 (d, J=8.28 Hz, 1H), 7.58 (d, J=8.28 Hz, 1H), 6.56 (s, 1H), 4.19 (s, 2H), 3.66-3.79 (m, 2H), 2.04 (d, J=5.77 Hz, 1H), 1.95 (d, J=14.05 Hz, 1H), 1.78-1.90 (m, 1H), 1.65-1.78 (m, 2H), 1.40-1.63 (m, 3H), 1.32 (s, 9H), 1.18 (s, 3H). MS (m/z) 448.3 (M+H+).

Workup

customthe vial was capped
filtrationThe reaction was filtered
custompurified

Sources & evidence

ORD record: ord-8d5172ecfdef444abe2bf1b336b288eb
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187464B2

Reaction notes

Loading…