HCID 117637152, compound → HCID 71522951, compound

HRID 2278373Notes

Reaction equation

HRID 2278373 reaction equation
Cl[C:2]1[N:3]=[C:4]2[CH:9]=[N:8][C:7]([S:10]([N:13]([CH2:49][CH2:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C@@H:14]([C:17]3[S:21][C:20]([C@@H:22]([NH:27][C:28](=[O:48])[C@H:29]([CH:35]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[NH:30][C:31]([O:33][CH3:34])=[O:32])[C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[CH2:15][OH:16])(=[O:12])=[O:11])=[CH:6][N:5]2[CH:55]=1>CO.[Pd]>[CH3:52][C:51]([CH3:54])([CH3:53])[CH2:50][CH2:49][N:13]([S:10]([C:7]1[N:8]=[CH:9][C:4]2[N:5]([CH:55]=[CH:2][N:3]=2)[CH:6]=1)(=[O:12])=[O:11])[C@@H:14]([C:17]1[S:21][C:20]([C@@H:22]([NH:27][C:28](=[O:48])[C@H:29]([CH:35]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[NH:30][C:31]([O:33][CH3:34])=[O:32])[C:23]([F:26])([F:24])[F:25])=[CH:19][CH:18]=1)[CH2:15][OH:16]

Participants

4

Reactant 1

HCID 117637152HCID 117637152, compound

Product 1

HCID 71522951HCID 71522951, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

To a suspension of Pd/C (25 mg, 0.235 mmol) in methanol (3 mL) under N2 was added N-[(1S)-1-{5-[(1R)-1-{[(2-chloroimidazo[1,2-a]pyrazin-6-yl)sulfonyl](3,3-dimethylbutyl)amino}-2-hydroxyethyl]thiophen-2-yl}-2,2,2-trifluoroethyl]-Nα-(methoxycarbonyl)-β-phenyl-L-phenylalaninamide (7.5 mg, 9.13 μmol). The resulting slurry was purged under vacuum and backfilled with H2 three times, after which the mixture was stirred for 16 hours at room temperature. Since LCMS showed only 50% conversion, the reaction mixture was transferred to a pressure flask and hydrogenated at 50 psi of H2 for 3 days, after which Pd/C (25 mg, 0.235 mmol) was added and the mixture was hydrogenated at 50 psi for 6 hours. The reaction mixture was filtered over a Celite pad, and the volatile components were evaporated under reduced pressure. The crude residue was purified by flash chromatography (Combiflash® Rf system; SiO2 4 grams Cat. No. 69-2203-304, solvent flow 18 mL/minute, elution gradient of 20-100% (EtOAc/hexanes). The fractions containing the desired product were pooled and evaporated under reduced pressure to afford the title material as a colorless oil. MS: m/z=787.2 ((MH+)).

Workup

  1. customThe resulting slurry was purged under vacuum
  2. waitthe reaction mixture was transferred to a pressure flask and hydrogenated at 50 psi of H2 for 3 days
  3. waitthe mixture was hydrogenated at 50 psi for 6 hours
  4. filtrationThe reaction mixture was filtered over a Celite pad
  5. customthe volatile components were evaporated under reduced pressure
  6. customThe crude residue was purified by flash chromatography (Combiflash® Rf system
  7. wash69-2203-304, solvent flow 18 mL/minute, elution gradient of 20-100% (EtOAc/hexanes)
  8. additionThe fractions containing the desired product
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9f54700e18dc4a28b77a37adba24bf75
Source dataset
uspto-grants-2015_09
Patent number
US09133157B2

Reaction notes

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