1,2-Dichloroethane → benzyl 4-{[({(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-11-yl}carbonyl)amino]sulfonyl}butanoate

HRID 421931Notes

Reaction equation

HRID 421931 reaction equation
[NH2:1][S:2]([CH2:5][CH2:6][CH2:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])(=[O:4])=[O:3].C(Cl)CCl.[C:22]([O:26][C:27]([NH:29][CH2:30][CH2:31][N:32]([CH3:61])[C@@H:33]1[CH2:40][N:39]2[C:41]3[CH:42]=[C:43]([C:54](O)=[O:55])[CH:44]=[CH:45][C:46]=3[C:47]([CH:48]3[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]3)=[C:38]2[C:37]2[CH:57]=[CH:58][CH:59]=[CH:60][C:36]=2[O:35][CH2:34]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:22]([O:26][C:27]([NH:29][CH2:30][CH2:31][N:32]([CH3:61])[C@@H:33]1[CH2:40][N:39]2[C:41]3[CH:42]=[C:43]([C:54]([NH:1][S:2]([CH2:5][CH2:6][CH2:7][C:8]([O:10][CH2:11][C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[O:9])(=[O:3])=[O:4])=[O:55])[CH:44]=[CH:45][C:46]=3[C:47]([CH:48]3[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]3)=[C:38]2[C:37]2[CH:57]=[CH:58][CH:59]=[CH:60][C:36]=2[O:35][CH2:34]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 66674687(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acidHCID 66674779Benzyl 4-sulfamoylbutanoate

Product 1

HCID 66674775benzyl 4-{[({(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-11-yl}carbonyl)amino]sulfonyl}butanoateYield 37%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Benzyl 4-(aminosulfonyl)butanoate (1.3 eq)(prepared as described in step 1), DMAP (2.5 eq) and EDC (1.5 eq), were added to a solution of (7R)-7-[{2-[(tert -butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid (0.03 M) in DCM. The reaction was stirred under N2 at RT for 24h, before volatiles were removed in vacuo to leave the crude product as a yellow gum, which was purified by automated RP-HPLC (WATERS XTERRA column; MeCN/H2O/0.1% TFA gradient). Fractions containing the pure compound were combined and lyophilized to afford the product as a white powder (37%). (ES+) m/z 787 (M+H)+

Workup

  1. customwere removed in vacuo
  2. customto leave the crude product as a yellow gum, which
  3. customwas purified by automated RP-HPLC (WATERS XTERRA column; MeCN/H2O/0.1% TFA gradient)
  4. additionFractions containing the pure compound

Sources & evidence

ORD record
ord-526224363ee24b428f90f684522f899b
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

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