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

HRID 2111595Notes

Reaction equation

HRID 2111595 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.[S:46]([NH2:50])([NH2:49])(=[O:48])=[O:47].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O.C(Cl)Cl>[NH2:49][S:46]([NH:50][C:43]([C:23]1[CH:22]=[CH:21][C:20]2[C:19]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]3)=[C:27]3[C:28]4[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][C:29]=4[CH:30]=[C:31]([C:33]([O:35][CH3:36])=[O:34])[CH2:32][N:26]3[C:25]=2[CH:24]=1)=[O:45])(=[O:48])=[O:47]

Participants

8

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 82267SulfamideHCID 5755909813-cyclohexyl-3-methoxy-6-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 57559091methyl 10-((aminosulfonyl)carbamoyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylateYield 91.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

1,1′-Carbonyldiimidazole (1.23 g, 7.60 mmol) was added to a slurry of 13-cyclohexyl-3-methoxy-6-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (2.6 g, 5.8 mmol) in THF (11 mL). The reaction mixture was heated at 60° C. for 1.5 h, cooled to rt, treated with sulfamide (1.12 g, 11.7 mmol), stirred 10 min and then treated with the dropwise addition of a solution of DBU (1.8 mL, 11.7 mmol) in THF (3 mL). The reaction mixture was stirred at rt for 3 h, diluted with EtOAc (80 mL) and CH2Cl2 (100 mL) and concentrated to dryness. The residue was diluted with CH2Cl2 (100 mL) and washed with 1N HCl (aq.) (2×100 mL). The combined aqueous layers were extracted with CH2Cl2 (100 mL) and the combined organic layers were washed with ½ saturated brine (˜50 mL), dried (MgSO4), filtered and concentrated. The residue was stirred with Et2O (˜75 mL) for 1 h and the solids were collected by filtration, rinsed with Et2O and dried to yield methyl 10-((aminosulfonyl)carbamoyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate (2.8 g, 5.3 mmol, 91%) as a bright yellow solid which was used without further purification. 1HNMR (300 MHz, CDCl3) δ 1.08-2.10 (m, 10H), 2.71-2.84 (m, 1H), 3.79 (s, 3H), 3.89 (s, 3H), 4.00-4.18 (m, 1H), 5.50-5.64 (m, 1H), 5.68 (s, 2H), 6.97 (d, J=2.6 Hz, 1H), 7.07 (dd, J=8.8, 2.6 Hz, 1H), 7.46 (dd, J=8.4, 1.5 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.78 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 8.10 (br s, 1H), 9.49 (s, 1H). LCMS: m/e 524 (M+H)+, ret time 3.60 min, column B, 4 minute gradient.

Workup

  1. temperaturecooled to rt
  2. stirringThe reaction mixture was stirred at rt for 3 h
  3. concentrationconcentrated to dryness
  4. additionThe residue was diluted with CH2Cl2 (100 mL)
  5. washwashed with 1N HCl (aq.) (2×100 mL)
  6. extractionThe combined aqueous layers were extracted with CH2Cl2 (100 mL)
  7. washthe combined organic layers were washed with ½ saturated brine (˜50 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. stirringThe residue was stirred with Et2O (˜75 mL) for 1 h
  12. filtrationthe solids were collected by filtration
  13. washrinsed with Et2O
  14. customdried

Sources & evidence

ORD record
ord-b831a4f9319142bd9041ba0c48c13196
Source dataset
uspto-grants-2009_04
Patent number
US07521444B2

Reaction notes

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