1,1'-Carbonyldiimidazole → methyl 13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate

HRID 1986006Notes

Reaction equation

HRID 1986006 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:13]1([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([C:43]([OH:45])=O)=[CH:24][C:25]=3[N:26]3[CH2:32][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:30][C:29]4[CH:37]=[C:38]([O:41][CH3:42])[CH:39]=[CH:40][C:28]=4[C:27]=23)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[CH3:46][CH:47]([S:49]([NH2:52])(=[O:51])=[O:50])[CH3:48].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[CH:13]1([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([C:43](=[O:45])[NH:52][S:49]([CH:47]([CH3:48])[CH3:46])(=[O:51])=[O:50])=[CH:24][C:25]=3[N:26]3[CH2:32][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:30][C:29]4[CH:37]=[C:38]([O:41][CH3:42])[CH:39]=[CH:40][C:28]=4[C:27]=23)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 3549191Propane-2-sulfonamideHCID 5755909813-cyclohexyl-3-methoxy-6-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 57559094methyl 13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylateYield 88.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

1,1′-Carbonyldiimidazole (262 mg, 1.62 mmol) was added to a slurry of 13-cyclohexyl-3-methoxy-6-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (603 mg, 1.36 mmol) in THF (3 mL). The reaction mixture was heated at 60° C. for 1.5 h, cooled to rt, treated with propane-2-sulfonamide (200 mg, 1.62 mmol), stirred 10 min and then treated with the dropwise addition of a solution of DBU (0.27 mL, 1.8 mmol) in THF (0.75 mL). The reaction mixture was stirred at rt overnight, diluted with EtOAc (15 mL) and washed with H2O (˜5 mL), 1N HCl (aq.) (2×10 mL) and brine (˜5 mL). The combined aqueous layers were extracted with EtOAc (15 mL) and the organic layer was washed with 1N HCl (aq.) (˜10 mL). The combined organic layers were washed with brine (˜5 mL), dried (MgSO4), filtered and concentrated. The residue was stirred with Et2O (˜15 mL) for 2 h and the solids were collected by filtration, rinsed with Et2O and dried to yield methyl 13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate (640 mg, 1.2 mmol, 85%) as a bright yellow solid which was used without further purification. 1HNMR (300 MHz, CDCl3) δ 1.12-2.13 (m, 10H), 1.47 (d, J=7.0 Hz, 6H), 2.73-2.86 (m, 1H), 3.82 (s, 3H), 3.89 (s, 3H), 4.06-4.26 (m, 1H), 4.09 (septet, J=7.0 Hz, 1H), 5.51-5.71 (m, 1H), 6.98 (d, J=2.6 Hz, 1H), 7.08 (dd, J=8.4, 2.6 Hz, 1H), 7.44 (dd, J=8.4, 1.5 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.80 (s, 1H), 7.87 (d, J=8.4 Hz, 1H), 8.10 (d, J=1.5 Hz, 1H), 8.57 (s, 1H). LCMS: m/e 551 (M+H)+, ret time 3.87 min, column B, 4 minute gradient.

Workup

  1. temperaturecooled to rt
  2. stirringThe reaction mixture was stirred at rt overnight
  3. washwashed with H2O (˜5 mL), 1N HCl (aq.) (2×10 mL) and brine (˜5 mL)
  4. extractionThe combined aqueous layers were extracted with EtOAc (15 mL)
  5. washthe organic layer was washed with 1N HCl (aq.) (˜10 mL)
  6. washThe combined organic layers were washed with brine (˜5 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. stirringThe residue was stirred with Et2O (˜15 mL) for 2 h
  11. filtrationthe solids were collected by filtration
  12. washrinsed with Et2O
  13. customdried

Sources & evidence

ORD record
ord-3b3c28c3b3944d7db2d8f3532377c49d
Source dataset
uspto-grants-2009_06
Patent number
US07547690B2

Reaction notes

Loading…