Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-methoxycarbonyl-propionylamino}-benzoic acid

HRID 384609Notes

Reaction equation

HRID 384609 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:35]2[CH:39]=[N:38][N:37]=[N:36]2)=[C:6](/[CH:8]=[CH:9]/[C:10]([NH:12][C@@H:13]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:14]([NH:16][C:17]2[CH:29]=[CH:28][C:20]([C:21]([O:23]C(C)(C)C)=[O:22])=[CH:19][CH:18]=2)=[O:15])=[O:11])[CH:7]=1.ClC1C=CC(N2C=NN=N2)=C(/C=C/C(O)=O)C=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CO.CCOC(C)=O.[Pd]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:35]2[CH:39]=[N:38][N:37]=[N:36]2)=[C:6](/[CH:8]=[CH:9]/[C:10]([NH:12][C@@H:13]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:14]([NH:16][C:17]2[CH:29]=[CH:28][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)=[O:15])=[O:11])[CH:7]=1

Participants

7

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66698416(2e)-3-[5-Chloro-2-(1h-tetrazol-1-yl)phenyl]-2-propenoic acidHCID 68475151(S,E)-tert-butyl 4-(2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamido)-4-methoxy-4-oxobutanamido)benzoate

Product 1

HCID 594021264-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-methoxycarbonyl-propionylamino}-benzoic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S,E)-tert-butyl 4-(2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamido)-4-methoxy-4-oxobutanamido)benzoate: 44BA was dissolved in MeOH (50 mL), treated with 5% Pd/C, and placed under hydrogen atmosphere (50 psi). After 12 h, the mixture was filtered through a plug of Celite® and the filter-cake was rinsed several times with MeOH. The combined filtrate was concentrated. The resulting oil was dissolved in THF (50 mL) and then (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylic acid (0.89 g, 3.56 mmol), BOP (1.57 g, 3.56 mmol), and TEA (1.48 mL, 10.67 mmol) were added at 25° C. with stirring. After 2 h, the reaction mixture was diluted with EtOAc, washed with water and then brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash chromatography (40 g column; (100% hexane/0% EtOAC to 0% hexane over 30 min) afforded 44BB (1.8 g, 55%) as a white solid. LCMS m/z 555 [M+H]+.

Workup

  1. filtrationthe mixture was filtered through a plug of Celite®
  2. washthe filter-cake was rinsed several times with MeOH
  3. concentrationThe combined filtrate was concentrated
  4. dissolutionThe resulting oil was dissolved in THF (50 mL)
  5. waitAfter 2 h
  6. washwashed with water
  7. dry with materialbrine, dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash chromatography (40 g column
  11. custom(100% hexane/0% EtOAC to 0% hexane over 30 min) afforded 44BB (1.8 g, 55%) as a white solid

Sources & evidence

ORD record
ord-32bdcb58b0c84e9ca116136dff1c1814
Source dataset
uspto-grants-2013_02
Patent number
US08367709B2

Reaction notes

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