Methanol → 1,1-Dimethylethyl 4-{6-methyl-5-[(1-methylethyl)oxy]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-piperidinecarboxylate

HRID 2064180Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[C:5]([CH3:12])=[CH:4][C:3]=1[NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.[CH3:27][OH:28]>O1CCCC1>[CH3:12][C:5]1[C:6]([O:8][CH:9]([CH3:10])[CH3:11])=[CH:7][C:2]2[NH:1][C:27](=[O:28])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]3)[C:3]=2[CH:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 1,1-dimethylethyl 4-({2-amino-5-methyl-4-[(1-methylethyl)oxy]phenyl}amino)-1-piperidinecarboxylate (D75) (0.16 mmol, 60 mg) in tetrahydrofuran (0.5 mL) was treated with N,N′-carbonyldiimidazole (0.24 mmol, 38.5 mg, 1.5 eq) under argon at room temperature, then the mixture was heated at 50° C. for 1 h, concentrated under reduced pressure, and the residue was treated with 10% aqueous sodium carbonate solution and extracted twice with ethyl acetate. The organics were combined, dried and concentrated under reduced pressure. The residue was finally purified by chromatography on silica (ethyl acetate/petrol ether then methanol) to give the title compound (0.14 mmol, 53 mg, 85% yield). M+H 390.3, 334.3, 316.3 (full molecule and fragments for loss of tert-butyl group and loss of Boc group).

Workup

concentrationconcentrated under reduced pressure
additionthe residue was treated with 10% aqueous sodium carbonate solution
extractionextracted twice with ethyl acetate
customdried
concentrationconcentrated under reduced pressure
customThe residue was finally purified by chromatography on silica (ethyl acetate/petrol ether

Sources & evidence

ORD record: ord-dfb0e1c9cac241f1a06079111d42083e
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288412B2

Reaction notes

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