Hydrochloric Acid → (S)-ethyl 2-(2-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)benzylthio)-1H-indol-3-yl)acetate

HRID 1471641Notes

Reaction equation

HRID 1471641 reaction equation
[C:1]([S:4][C:5]1[NH:6][C:7]2[C:12]([C:13]=1[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:11][CH:10]=[CH:9][CH:8]=2)(=O)[CH3:2].[OH-].[K+].Cl[CH2:23][C:24]1[CH:25]=[C:26]([CH2:30][C@H:31]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[C:32]([N:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH3:35])=[O:33])[CH:27]=CC=1.Cl>C(O)C>[C:47]([O:46][C:45]([NH:44][C@H:31]([C:32]([N:34]([C:36]1[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=1)[CH3:35])=[O:33])[CH2:30][C:26]1[CH:27]=[C:2]([CH:23]=[CH:24][CH:25]=1)[CH2:1][S:4][C:5]1[NH:6][C:7]2[C:12]([C:13]=1[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:51])([CH3:49])([CH3:50])[CH3:48]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 90281395ethyl 2-(2-(acetylthio)-1H-indol-3-yl)acetateHCID 90289957(5)-Tert-butyl 3-(3-(chloromethyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 90327422(S)-ethyl 2-(2-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)benzylthio)-1H-indol-3-yl)acetateYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution ethyl 2-(2-(acetylthio)-1H-indol-3-yl)acetate (380 mg, 1.4 mmol) in ethanol (5 ml) was added potassium hydroxide (84 mg, 1.5 mmol). After 10 minutes, (5)-tert-butyl 3-(3-(chloromethyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (I-5, 605 mg, 1.4 mmol) was added to the solution. The reaction was stirred for 2 hours and then neutralized with 1N (aq) HCl and then extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was introduced to a silica gel loading column and purified by column chromatography (1-5% MeOH/DCM) to provide the desired product (796 mg, 1.26 mmol), 90%. MS (m/z) 632 [M+H]+.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe crude product was introduced to a silica gel loading column
  6. custompurified by column chromatography (1-5% MeOH/DCM)

Sources & evidence

ORD record
ord-d21a0659b469446bbb4c036efbceb50d
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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