1,1'-Carbonyldiimidazole → N-(5-tert-Butyl-1,2-oxazol-3-yl)-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamide

HRID 1521762Notes

Reaction equation

[O:1]=[C:2]1[NH:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]3[N:15]=[C:14]([C:16]([OH:18])=O)[CH:13]=[CH:12][C:10]=3[CH:11]=[C:3]12.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:31]([C:35]1[O:39][N:38]=[C:37]([NH2:40])[CH:36]=1)([CH3:34])([CH3:33])[CH3:32].C1CCN2C(=NCCC2)CC1>C1COCC1.CN1C(=O)CCC1>[C:31]([C:35]1[O:39][N:38]=[C:37]([NH:40][C:16]([C:14]2[CH:13]=[CH:12][C:10]3[CH:11]=[C:3]4[C:2](=[O:1])[NH:8][CH2:7][CH2:6][CH2:5][N:4]4[C:9]=3[N:15]=2)=[O:18])[CH:36]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate E, 35 mg, 0.14 mmol) in THF (2 mL) and NMP (0.5 mL) is added 1,1′-carbonyldiimidazole (58 mg, 0.36 mmol). The mixture is stirred at 60° C. for 1 h and is then cooled to room temperature. 5-tert-Butyl-3-aminoisoxazole (80 mg, 0.57 mmol) and DBU (53 μL, 0.36 mmol) are added and the mixture is stirred at 60° C. for 16 h. The mixture is cooled to room temperature and the THF is removed in vacuo. The residue is purified via preparative HPLC using a gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA to afford the title compound (6 mg, 11%). LCMS: 368.20 (M+H+). (System V-med polar)

Workup

temperatureis then cooled to room temperature
stirringthe mixture is stirred at 60° C. for 16 h
temperatureThe mixture is cooled to room temperature
customthe THF is removed in vacuo
customThe residue is purified via preparative HPLC
washa gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA

Sources & evidence

ORD record: ord-5657bc87649242faae2dd8aae6a3fa6d
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073926B2

Reaction notes

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