Water → HCID 66988966, compound

HRID 1917611Notes

Reaction equation

[CH3:1][C:2]([CH3:28])([CH3:27])[C:3]([C:5]1[C:6]([CH3:26])=[C:7]([C:17]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4].[C:29]([O:33][CH3:34])(=[O:32])[CH:30]=[CH2:31].C1CCN2C(=NCCC2)CC1.O>CN(C=O)C>[CH3:28][C:2]([CH3:1])([CH3:27])[C:3]([C:5]1[C:6]([CH3:26])=[C:7]([C:17]([N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:31][CH2:30][C:29]([O:33][CH3:34])=[O:32])=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 1-(2,2-dimethylpropanoyl)-2-methyl-N-phenyl-7-(propan-2-yl)indolizine-3-carboxamide (70 mg, 0.19 mmol) in DMF (2.0 mL) is added Triton B (8 μl, 0.02 mmol) followed by methyl acrylate (18 μl, 0.20 mmol). The reaction is stirred for 3 days at 23° C. after which time DBU (0.20 mL, 1.31 mmol) and additional methyl acrylate (0.10 mL, 1.11 mmol) are introduced. The reaction is heated at 50° C. for 18 h and then cooled to 23° C., poured into water, extracted with EtOAc, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 30% EtOAc in hexanes) gives methyl N-{[1-(2,2-dimethylpropanoyl)-2-methyl-7-(propan-2-yl)indolizin-3-yl]carbonyl}-N-phenyl-beta-alaninate (60 mg, 70%).

Workup

additionare introduced
temperaturecooled to 23° C.
extractionextracted with EtOAc
dry with materialdried with MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the crude by flash chromatography (SiO2, hexanes to 30% EtOAc in hexanes)

Sources & evidence

ORD record: ord-fe731fffa6354781af49a7f8227dec8f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618300B2

Reaction notes

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