Acetaldehyde → N-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-4-(2-ethylamino-2-methyl-propoxy)-phenyl]-3-trifluoromethyl-benzamide

HRID 1507079Notes

Reaction equation

HRID 1507079 reaction equation
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:2].[Na+].[NH2:15][C:16]([CH3:46])([CH3:45])[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:37])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=2)=[CH:21][C:20]=1[C:38]1[N:39]([CH3:44])[N:40]=[CH:41][C:42]=1[Cl:43].C(=O)C.FC(F)(F)C([O-])=O>C1COCC1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[Cl:43][C:42]1[CH:41]=[N:40][N:39]([CH3:44])[C:38]=1[C:20]1[CH:21]=[C:22]([NH:25][C:26](=[O:37])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:34])[F:35])[CH:28]=2)[CH:23]=[CH:24][C:19]=1[O:18][CH2:17][C:16]([NH:15][CH2:1][CH3:2])([CH3:46])[CH3:45]

Participants

8

Reactant 4

HCID 177AcetaldehydeHCID 84468TrifluoroacetateHCID 5049666Sodium triacetoxyborohydrideHCID 57814739N-(4-(2-amino-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 24888500N-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-4-(2-ethylamino-2-methyl-propoxy)-phenyl]-3-trifluoromethyl-benzamideYield 22%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Sodium triacetoxyborohydride (34.2 mg, 161 μmol) was added to a solution of N-(4-(2-amino-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamide (53.8 mg, 115 μmol) and acetaldehyde (5.08 mg, 115 μmol) in THF (0.5 mL), and the mixture was stirred at room temperature. After 4 hours, the reaction was quenched with saturated sodium bicarbonate and extracted with dichloromethane. The extract was evaporated to dryness, the residue was redissolved in methanol, and the product was isolated by preparative HPLC. The trifluoroacetate salt was dissolved in a mixture of ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried with sodium sulfate, and evaporated to dryness to afford the title compound (12.5 mg, 22%). LCMS m/z (%)=497.5 (M+H, 37Cl 45.4), 495.3 (M+H, 35Cl 100.0%). 1H NMR (400 MHz, MeOH-d4) δ 1.00 (t, J=7.07 Hz, 3H) 1.07 (s, 6H) 2.42-2.51 (m, 2H) 3.71 (s, 3H) 3.85-3.88 (m, J=9.35 Hz, 1H) 3.90 (d, J=9.09 Hz, 1H) 7.22 (d, J=9.09 Hz, 1H) 7.58 (s, 1H) 7.67 (d, J=2.78 Hz, 1H) 7.73 (t, J=7.83 Hz, 1H) 7.85-7.92 (m, 2H) 8.21 (d, J=7.83 Hz, 1H) 8.27 (s, 1H).

Workup

  1. customthe reaction was quenched with saturated sodium bicarbonate
  2. extractionextracted with dichloromethane
  3. customThe extract was evaporated to dryness
  4. dissolutionthe residue was redissolved in methanol
  5. customthe product was isolated by preparative HPLC
  6. washThe organic layer was washed with brine
  7. dry with materialdried with sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-a26a66e22ca04ff89e2ba02fee2c8a79
Source dataset
uspto-grants-2015_12
Patent number
US09221755B2

Reaction notes

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