Methanol → HCID 71227585, compound

HRID 715531Notes

Reaction equation

C(=O)([O:7][CH2:8][C:9]([C:12]1[CH:16]=[C:15]([N:17]2[CH2:21][C@@:20]3([CH2:26][CH2:25][CH2:24][C@@:23]([CH2:28][N:29]4[C:33]5[CH:34]=[C:35]([C:38]#[N:39])[CH:36]=[CH:37][C:32]=5[N:31]=[CH:30]4)([CH3:27])[CH2:22]3)[O:19][C:18]2=[O:40])[O:14][N:13]=1)([CH3:11])[CH3:10])OC(C)(C)C.C([O-])([O-])=O.[K+].[K+].O.CO>CC#N.O>[OH:7][CH2:8][C:9]([C:12]1[CH:16]=[C:15]([N:17]2[CH2:21][C@@:20]3([CH2:26][CH2:25][CH2:24][C@@:23]([CH2:28][N:29]4[C:33]5[CH:34]=[C:35]([C:38]#[N:39])[CH:36]=[CH:37][C:32]=5[N:31]=[CH:30]4)([CH3:27])[CH2:22]3)[O:19][C:18]2=[O:40])[O:14][N:13]=1)([CH3:11])[CH3:10]

Participants

Conditions

Temperature: 110 °C

Procedure

To a 2 mL microwave vial was added tert-butyl (2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)isoxazol-3-yl)-2-methylpropyl) carbonate (30 mg, 0.053 mmol), K2CO3 (5.15 μg, 0.037 μmol), water (0.500 mL) and MeOH (0.5 mL). The vial was capped and heated to 110° C. for 3 h. The mixture was then filtered through paper, and the paper washed with MeOH (2 mL), then concentrated. This mixture was purified on reverse phase Gilson HPLC: 30 mm×150 mm Waters Sunfire column, neutral conditions 10-100% MeCN/H2O, 14 min, 40 mL/min to give 1-(((5S,7S)-3-(3-(1-hydroxy-2-methylpropan-2-yl)isoxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white solid (6.2 mg, 24% yield). MS (m/z) 464.3 (M+H+).

Workup

customThe vial was capped
filtrationThe mixture was then filtered through paper
washthe paper washed with MeOH (2 mL)
concentrationconcentrated
customThis mixture was purified on reverse phase Gilson HPLC

Sources & evidence

ORD record: ord-0ac74903eca94711ab94d07eeea54c95
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187464B2

Reaction notes

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