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

HRID 1471634Notes

Reaction equation

HRID 1471634 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][C:14]([O-:16])=[O:15])=[C:5]1[CH2:17][S:18][C:19](=O)[CH3:20])(=O)C.[OH-].[K+].Cl[CH2:25][C:26]1[CH:27]=[C:28]([CH2:32][C@H:33]([NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])[C:34]([N:36]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=2)[CH3:37])=[O:35])[CH:29]=CC=1.Cl.[CH2:55](O)[CH3:56]>>[C:49]([O:48][C:47]([NH:46][C@H:33]([C:34]([N:36]([C:38]1[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=1)[CH3:37])=[O:35])[CH2:32][C:28]1[CH:29]=[C:20]([CH:25]=[CH:26][CH:27]=1)[CH2:19][S:18][CH2:17][C:5]1[NH:4][C:12]2[C:7]([C:6]=1[CH2:13][C:14]([O:16][CH2:55][CH3:56])=[O:15])=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:53])([CH3:50])([CH3:51])[CH3:52]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 90289957(5)-Tert-butyl 3-(3-(chloromethyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 1317327522-(1-acetyl-2-(acetylthiomethyl)-1H-indol-3-yl)acetate

Product 1

HCID 131732751(S)-ethyl 2-(2-((3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)benzylthio)methyl)-1H-indol-3-yl)acetate

Procedure

To a solution 2-(1-acetyl-2-(acetylthiomethyl)-1H-indol-3-yl)acetate (392 mg, 1.17 mmol) in ethanol (10 ml), was added potassium hydroxide (0.13 g, 2.32 mmol). After 10 minutes, (S)-tert-butyl 3-(3-(chloromethyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (507 mg, 1.17 mmol) was added to the solution. The reaction was stirred for 2 hours and then neutralized with 1N (aq) HCl. The mixture was 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 (3-6% MeOH/DCM) to provide the desired product (650 mg, 1.0 mmol), 85%. MS (m/z) 646 [M+H]+.

Workup

  1. extractionThe mixture was extracted 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 (3-6% MeOH/DCM)

Sources & evidence

ORD record
ord-d5d51ce08026486e92785a233ba93bc9
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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