N,N-Dimethylsulfamide → 13-Cyclohexyl-n-[(dimethylamino)sulfonyl]-6,7-dihydro-(5r,6s)-rel-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 860741Notes

Reaction equation

HRID 860741 reaction equation
Cl.CN(C)CCCN=C=NCC.[CH:13]1([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([C:39](O)=[O:40])=[CH:24][C:25]=3[N:26]3[CH2:32][C@H:31]([OH:33])[C@H:30]([OH:34])[C:29]4[CH:35]=[CH:36][CH:37]=[CH:38][C:28]=4[C:27]=23)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[CH3:42][N:43]([CH3:48])[S:44]([NH2:47])(=[O:46])=[O:45]>CN(C1C=CN=CC=1)C.CN(C=O)C.C(Cl)Cl>[CH:13]1([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([C:39]([NH:47][S:44]([N:43]([CH3:48])[CH3:42])(=[O:46])=[O:45])=[O:40])=[CH:24][C:25]=3[N:26]3[CH2:32][C@H:31]([OH:33])[C@H:30]([OH:34])[C:29]4[CH:35]=[CH:36][CH:37]=[CH:38][C:28]=4[C:27]=23)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 3

HCID 134472N,N-DimethylsulfamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69207235(5R,6S)-rel-13-Cyclohexyl-6,7-dihydro-5,6-dihydroxy-5H-indolo[2,1-a}[2]benzazepine-10-carboxylic acid

Product 1

HCID 6920646513-Cyclohexyl-n-[(dimethylamino)sulfonyl]-6,7-dihydro-(5r,6s)-rel-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (12.6 mg, 0.066 mmol) was added to a solution of 13-cyclohexyl-6,7-dihydro-(5R,6S)-rel-5,6-dihydroxy-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (8.7 mg, 0.022 mmol) and DMAP (8.1 mg, 0.066 mmol) in DMF (0.3 mL) and CH2Cl2 (0.3 mL) at 22° C. The vial was shaken for a minute at 22° C. then N,N-dimethylsulfamide (5.5 mg, 0.044 mmol) was added. Stirring was continued for 18 hr. The solution was then filtered and purified by Prep. reverse phase chromatography. The product containing fraction was concentrated on a Speed Vac® to leave the title compound as a white film (1.2 mg, 11%). ESI-MS m/z 498 (MH+) 1H NMR (500 MHz, MeOD) δ 1.23–1.33 (m, 1 H) 1.39–1.54 (m, 2 H) 1.62 (m, 1 H) 1.77–1.87 (m, 2 H) 1.93–2.18 (m, 4 H) 2.99 (d, J=11.29 Hz, 1 H) 3.04 (s, 6 H) 3.35 (m, 1 H) 4.42 (d, J=4.58 Hz, 1 H) 4.56 (m, 1 H) 4.75 (dd, J=14.50, 7.17 Hz, 1 H) 7.47 (m, 2 H) 7.54 (m, 1 H) 7.61 (dd, J=8.55, 1.53 Hz, 1 H) 7.80 (d, J=7.63 Hz, 1 H) 7.94 (d, J=8.85 Hz, 1 H) 8.13 (s, 1 H).

Workup

  1. stirringStirring
  2. filtrationThe solution was then filtered
  3. custompurified by Prep
  4. additionThe product containing fraction
  5. concentrationwas concentrated on a Speed Vac®

Sources & evidence

ORD record
ord-2fcf3d0255544890be9278597b5101f6
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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