3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-N,N-dimethyl-propionamide → HCID 11753944, compound

HRID 346893Notes

Reaction equation

HRID 346893 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:16]([N:23]3[CH2:31][C:30]4[C:25](=[C:26]([N+:32]([O-])=O)[CH:27]=[CH:28][CH:29]=4)[C:24]3=[O:35])[CH2:17][C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:15])[F:14])[CH2:3][CH2:2]1.[H][H]>C(OCC)(=O)C.[Pd]>[NH2:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]2[C:25]=1[C:24](=[O:35])[N:23]([CH:16]([C:8]1[CH:9]=[CH:10][C:11]([O:12][CH:13]([F:14])[F:15])=[C:6]([O:5][CH2:4][CH:1]3[CH2:2][CH2:3]3)[CH:7]=1)[CH2:17][C:18]([N:20]([CH3:21])[CH3:22])=[O:19])[CH2:31]2

Participants

5

Reactant 2

HCID 104356303-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-N,N-dimethyl-propionamideHCID 178418361HCID 178418361, compound

Product 1

HCID 11753944HCID 11753944, compoundYield 97.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-N,N-dimethyl-propionamide (330 mg, 0.67 mmol) in ethyl acetate (100 ml) was added 10% Pd on carbon (100 mg). The suspension was shaked under about 50 psi hydrogen atmosphere at room temperature overnight. The suspension was filtered through a pad of celite. The solvent was removed and the resulted oil was purified by HPLC (CH3CN:water=40:60) to give 3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-N,N-dimethyl-propionamide as a white solid (300 mg, 65%): mp 70–72° C.; 1HNMR (CDCl3): δ 0.31–0.37 (m, 2H), 0.58–0.65 (m, 2H), 1.21–1.28 (m, 1H), 2.90(s, 3H), 3.05 (dd, J=6.3, 15.8 Hz, 1H), 3.09 (s, 3H), 3.52 (dd, J=8.5, 15.3 Hz, 1H), 3.85 (d, J=7 Hz, 2H), 4.20 (d, J=16.8 Hz, 1H), 4.35 (d, J=16.8 Hz, 1H), 5.20 (broad, 2H), 5.56 (dd, J=6.3, 8.5 Hz, 1H), 6.52–6.63 (m, 2H), 6.59 (t, JH-F=75 Hz, 1H), 6.90–6.98 (m, 1H), 7.09–7.26 (m, 3H); 13C NMR (CDCl3): δ 10.8, 36.2, 37.0, 38.1, 49.8, 54.3, 114.0, 114.9, 116.3, 116.9, 120.1, 121.0, 123.3, 133.4, 139.4, 140.5, 143.4, 146.6, 151.3, 170.4, 170.9; Anal. Calcd. for C24H27F2N3O4 +0.18 H2O: C, 62.30; H, 5.96; N, 9.08; H2O 0.7. Found: C, 62.30; H, 5.89; N, 9.02; H2O, 0.7.

Workup

  1. filtrationThe suspension was filtered through a pad of celite
  2. customThe solvent was removed
  3. customthe resulted oil was purified by HPLC (CH3CN:water=40:60)

Sources & evidence

ORD record
ord-deeb7d9f9cd84c71ac2e6a6de4ec4a3a
Source dataset
uspto-grants-2007_02
Patent number
US07173058B2

Reaction notes

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