HCID 131732754, compound → HCID 131732753, compound

HRID 1471652Notes

Reaction equation

HRID 1471652 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:36]([N:38]([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)[CH3:39])=[O:37])[CH2:10][C:11]1[CH:12]=[C:13]([CH:33]=[CH:34][CH:35]=1)[CH:14]=[CH:15][C:16]1[NH:24][C:23]2[C:18](=[N:19][C:20]([O:25][CH3:26])=[CH:21][CH:22]=2)[C:17]=1[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:36]([N:38]([C:40]1[CH:41]=[CH:42][C:43]([Cl:46])=[CH:44][CH:45]=1)[CH3:39])=[O:37])[CH2:10][C:11]1[CH:12]=[C:13]([CH:33]=[CH:34][CH:35]=1)[CH2:14][CH2:15][C:16]1[NH:24][C:23]2[C:18](=[N:19][C:20]([O:25][CH3:26])=[CH:21][CH:22]=2)[C:17]=1[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 131732754HCID 131732754, compound

Product 1

HCID 131732753HCID 131732753, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(S)-ethyl 2-(2-(3-(2-(tert-butoxycarbonylamino)-3-((4-chlorophenyl)(methyl)amino)-3-oxopropyl)styryl)-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetate (170 mg, 0.26 mmol) was dissolved in 50 mL of ethyl acetate and purged with nitrogen. Rhodium (5 wt. % on alumina powder, 60 mg) was added. The reaction mixture was purged with hydrogen and stirred at ambient temperature overnight under a hydrogen balloon. After completion of the reaction, the mixture was filtered, rinsing with ethyl acetate. The filtrate was concentrated to afford (S)-ethyl 2-(2-(3-(2-(tert-butoxycarbonylamino)-3-((4-chlorophenyl)(methyl)amino)-3-oxopropyl)phenethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetate which was dissolved in 5 mL of THF/MeOH/H2O (3/2/1), and to it was added LiOH.H2O (55 mg). The reaction mixture was allowed to stir at ambient temperature for two hours and then purified by RP HPLC eluting with acetonitrile/water (with 0.1% TFA) to afford (S)-2-(2-(3-(2-(tert-butoxycarbonylamino)-3-((4-chlorophenyl)(methyl)amino)-3-oxopropyl)phenethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetic acid. The compound was dissolved in 3 mL of 10% TFA/CH2Cl2 and stirred at ambient temperature for two hours. The reaction was cooled down to 0° C. and quenched with 0.3 mL of pyridine. The solvent was removed and the residue was purified by RP HPLC eluting with acetonitrile and water to afford 106 mg of (S)-2-(2-(3-(2-amino-3-((4-chlorophenyl)(methyl)amino)-3-oxopropyl)phenethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetic acid. MS (m/z): 521.3 [M+H]+; HPLC retention time 2.05 min (5-99% acetonitrile:water with 0.05% formic acid).

Workup

  1. custompurged with nitrogen
  2. additionRhodium (5 wt. % on alumina powder, 60 mg) was added
  3. customThe reaction mixture was purged with hydrogen
  4. customAfter completion of the reaction
  5. filtrationthe mixture was filtered
  6. washrinsing with ethyl acetate
  7. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-58c70393a16d449aa5842b130d7fd1ac
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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