2,4-Dimethylbenzaldehyde → HCID 10371682, compound

HRID 1391982Notes

Reaction equation

HRID 1391982 reaction equation
[C:1]([O:5][C:6](=[O:45])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1[C:18](=[O:44])[NH:19][C@H:20]1[CH2:24][CH2:23][N:22]([C@@H:25]([CH2:31][NH:32][C:33](OCC2C=CC=CC=2)=O)[C@@H:26]([OH:30])[C:27]#[C:28][CH3:29])[C:21]1=[O:43])([CH3:4])([CH3:3])[CH3:2].[CH3:46][C:47]1[CH:54]=[C:53]([CH3:55])[CH:52]=[CH:51][C:48]=1C=O.C([BH3-])#N.[Na+]>CO.[Pd]>[C:1]([O:5][C:6](=[O:45])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:16])([F:15])[F:17])=[CH:10][C:9]=1[C:18](=[O:44])[NH:19][C@H:20]1[CH2:24][CH2:23][N:22]([C@@H:25]([CH2:31][NH:32][CH2:33][C:48]2[CH:51]=[CH:52][C:53]([CH3:55])=[CH:54][C:47]=2[CH3:46])[C@@H:26]([OH:30])[CH2:27][CH2:28][CH3:29])[C:21]1=[O:43])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 618142,4-DimethylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69292167HCID 69292167, compound

Product 1

HCID 10371682HCID 10371682, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The compound (2-{(3S)-1-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (87 mg, 0.14 mmol) was dissolved in MeOH (4 mL). The resultant solution was charged with 5% Pd/C, Degussa style (10 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was redissolved in MeOH (4 mL). The resultant solution was charged sequentially with 2,4-dimethylbenzaldehyde (0.015 mL, 0.11 mmol) and sodium cyanoborohydride (10 mg), stirred for 12 h at RT, quenched with sat. NaHCO3, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by reverse-phase HPLC afforded the title compound as a white powder after lyopholization (15 mg). MS found: (M+H)+=621.5.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was redissolved in MeOH (4 mL)
  4. stirringstirred for 12 h at RT
  5. customquenched with sat. NaHCO3
  6. extractionextracted twice with EtOAc
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by reverse-phase HPLC

Sources & evidence

ORD record
ord-082b0b1f8b9b4a3fb192ef08e29048d4
Source dataset
uspto-grants-2008_03
Patent number
US07338975B2

Reaction notes

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