(5)-tert-butyl 2-(3-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)prop-1-enyl)-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate → (S)-2-(2-(3-(3-(2-amino-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)propyl)-1H-indol-3-yl)acetic acid

HRID 1471626Notes

Reaction equation

HRID 1471626 reaction equation
C(OC([NH:8][C@H:9]([C:42]([N:44]([C:46]1[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=1)[CH3:45])=[O:43])[CH2:10][C:11]1[CH:12]=[C:13]([CH2:17][CH:18]=[CH:19][C:20]2[N:21](C(OC(C)(C)C)=O)[C:22]3[C:27]([C:28]=2[CH2:29][C:30]([O:32]CC)=[O:31])=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:14]=[CH:15][CH:16]=1)=O)(C)(C)C>[Pd].C(O)C.CCOC(C)=O>[NH2:8][C@H:9]([C:42]([N:44]([C:46]1[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[CH:50][CH:51]=1)[CH3:45])=[O:43])[CH2:10][C:11]1[CH:12]=[C:13]([CH2:17][CH2:18][CH2:19][C:20]2[NH:21][C:22]3[C:27]([C:28]=2[CH2:29][C:30]([OH:32])=[O:31])=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 1

HCID 90281387(5)-tert-butyl 2-(3-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)prop-1-enyl)-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate

Product 1

HCID 90281297(S)-2-(2-(3-(3-(2-amino-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)propyl)-1H-indol-3-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of (5)-tert-butyl 2-(3-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)prop-1-enyl)-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate (178 mg, 0.24 mmol) and palladium on carbon (134 mg, 10%) in 2.5 ml of ethanol and 2.5 ml of EtOAc, was degassed with nitrogen. The reaction was stirred at room temperature for 3 hours under an atmosphere of H2 at 1 atm. The suspension was purged with nitrogen and filtered through celite. The filtrate was concentrated and the crude product was used without further purification. MS (m/z) 728 [M+H]+. The crude product was redissolved in 1 ml of tetrahydrofuran and 1 ml of methanol and 2 ml of 2N (aq.) lithium hydroxide was added to the solution. The solution was heated at 60° C. for 2 hours. The solution was cooled in an ice bath and acidified with 1N (aq) HCl. The resulting mixture was extracted with EtOAc (2×25 ml). The organic layer was dried over Na2SO4, filtered and concentrated. TFA (2 ml) was added to the crude product. After 20 minutes, the solvent was removed and the residue was dried under high vacuum. The crude product was used without further purification. The crude product yield was (100 mg, 0.2 mmol). MS (m/z) 500 [M+H]+.

Workup

  1. customwas degassed with nitrogen
  2. customThe suspension was purged with nitrogen
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated
  5. customthe crude product was used without further purification
  6. dissolutionThe crude product was redissolved in 1 ml of tetrahydrofuran
  7. addition1 ml of methanol and 2 ml of 2N (aq.) lithium hydroxide was added to the solution
  8. temperatureThe solution was heated at 60° C. for 2 hours
  9. temperatureThe solution was cooled in an ice bath
  10. extractionThe resulting mixture was extracted with EtOAc (2×25 ml)
  11. dry with materialThe organic layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionTFA (2 ml) was added to the crude product
  15. waitAfter 20 minutes
  16. customthe solvent was removed
  17. customthe residue was dried under high vacuum
  18. customThe crude product was used without further purification

Sources & evidence

ORD record
ord-142db65e5ce3475aa588ff62a66858ca
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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