1,2-Dichloroethane → tert-butyl (3S)-3-[{(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]pyrrolidine-1-carboxylate

HRID 1669466Notes

Reaction equation

HRID 1669466 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C@H:12]([N:15]([CH3:45])[C@@H:16]2[CH2:23][N:22]3[C:24]4[CH:25]=[C:26]([C:37](OC)=[O:38])[CH:27]=[CH:28][C:29]=4[C:30]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[C:21]3[C:20]3[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=3[O:18][CH2:17]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.C(Cl)CCl.[CH3:51][O:52][CH:53]([O:61][CH3:62])[CH2:54][N:55]([CH3:60])[S:56]([NH2:59])(=[O:58])=[O:57]>O1CCOCC1.C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:31]1([C:30]2[C:29]3[CH:28]=[CH:27][C:26]([C:37]([NH:59][S:56]([N:55]([CH2:54][CH:53]([O:52][CH3:51])[O:61][CH3:62])[CH3:60])(=[O:58])=[O:57])=[O:38])=[CH:25][C:24]=3[N:22]3[C:21]=2[C:20]2[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=2[O:18][CH2:17][C@H:16]([N:15]([CH3:45])[C@H:12]2[CH2:13][CH2:14][N:10]([C:8]([O:7][C:3]([CH3:4])([CH3:6])[CH3:5])=[O:9])[CH2:11]2)[CH2:23]3)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 67346364methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateHCID 86627889N-(2,2-dimethoxyethyl)-N-methylsulfamide

Product 1

HCID 67344852tert-butyl (3S)-3-[{(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

1M KOH (3.5 eq) was added to a 0.3M solution of methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (1 eq) in dioxane and the mixture was stirred at 75° C. for 12 h. The pH was adjusted at 0° C. by addition of 1N HCl (until pH=6), then all volatiles were evaporated, the solid residue was taken in CHCl3 and salt was filtered off. The filtrate was concentrated in vacuo to afford a residue that was taken in dry DCM (0.05M); DMAP (3.5 eq), EDC (1.5 eq) and N-(2,2-dimethoxyethyl)-N-methylsulfamide (1.5 eq; prepared as described in Example 1, step 1) were added and the mixture was stirred at 40° C. for 1 h. The residue obtained after evaporation was extracted with EtOAc. The combined organic phases were washed with 1M HCl, sat. aq. NaHCO3 and brine, dried over Na2SO4 and concentrated to afford the title compound which was used without further purification. (ES+) m/z 754 (M+H)+.

Workup

  1. customall volatiles were evaporated
  2. filtrationsalt was filtered off
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto afford a residue that
  5. stirringthe mixture was stirred at 40° C. for 1 h
  6. customThe residue obtained
  7. customafter evaporation
  8. extractionwas extracted with EtOAc
  9. washThe combined organic phases were washed with 1M HCl, sat. aq. NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6aa9a0985fb445bfb39565bac8ac94b1
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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