3-Bromo-1-propanol → 8-Carbamoylmethoxy-3-(4-fluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester

HRID 736093

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([O:20]CCCO)[CH:17]=[CH:18][C:19]=3[C:11]=2[C:10]([CH3:26])([CH3:25])[CH2:9][N:8]([C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30](F)[CH:29]=2)[CH:7]=1)=[O:5])[CH3:2].C(OC(C1C2NC3C=C(O)C=CC=3C=2C(C)(C)C[N:44]([C:59](=[O:67])[C:60]2C=CC(F)=CC=2)C=1)=O)C.C(N(C(C)C)CC)(C)C.BrCCCO>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([O:20][CH2:60][C:59](=[O:67])[NH2:44])[CH:17]=[CH:18][C:19]=3[C:11]=2[C:10]([CH3:26])([CH3:25])[CH2:9][N:8]([C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 75 °C

Procedure

To prepare 3-(3,4-difluoro-benzoyl)-1,1-dimethyl-8-(3-hydroxy-propoxy)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester, a mixture of 3-(4-fluorobenzoyl)-8-hydroxy-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]-indole-5-carboxylic acid ethyl ester (46 mg, 0.11 mmol), diisopropylethylamine (0.5 mL), and 3-bromo-1-propanol (1.4 mL) in dry acetonitrile (1 mL) was stirred at 75° C. for 10 hours. The solvent was removed in vacuo, and the residue was purified by preparative reverse-phase HPLC, which was then acylated in the manner described in Example 2A. 1HNMR (CDCl3): δ 10.51 (1H, s), 7.86 (1H, s), 7.82 (1H, d), 7.66-7.59 (2H, m), 7.15-7.09 (2H, m), 6.87 (1H, d), 6.74 (1H, m), 4.27-4.15 (4H, m), 4.09 (2H, brs), 3.90 (2H, m), 2.11-2.05 (2H, m), 1.60 (6H, s), 1.26-1.21 (3H, m). MS (ES): 481 (MH+).

Workup

customThe solvent was removed in vacuo
customthe residue was purified by preparative reverse-phase HPLC, which

Sources & evidence

ORD record: ord-a40e2cf3400a4a4f8a1269f5b2cb9cc5
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595311B2

Linked notes

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