Butanal → N-[4-(2-Butylamino-2-methyl-propoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 1685685Notes

Reaction equation

HRID 1685685 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[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].[CH:47](=O)[CH2:48][CH2:49][CH3:50].C(Cl)(=O)C>C1COCC1.CO>[CH2:47]([NH: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:34])[F:35])[CH:28]=2)=[CH:21][C:20]=1[C:38]1[N:39]([CH3:44])[N:40]=[CH:41][C:42]=1[Cl:43])[CH2:48][CH2:49][CH3:50]

Participants

7

Reactant 4

HCID 261ButanalHCID 6367Acetyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 57814739N-(4-(2-amino-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 24890539N-[4-(2-Butylamino-2-methyl-propoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethyl-benzamideYield 39.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium triacetoxyborohydride (34 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 butyraldehyde (8 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 products were isolated by preparative HPLC. Product containing fractions were combined and concentrated in a vacuum centrifuge to one fourth of the original volume. The solution was made alkaline with saturated sodium bicarbonate, the product was extracted with dichloromethane, and the extract was evaporated to dryness. The residue was dissolved in a solution of acetyl chloride (16 μl, 230 μmol) in methanol (1 mL) and evaporated to dryness. The residue was dissolved in water and lyophilized to give the title compound (24 mg, 37%) as the hydrochloride salt. LCMS m/z (%)=553.6 (M+H, 37Cl 34.5), 551.6 (M+H, 35Cl 100.0%). 1H NMR (400 MHz, DMSO-d6) δ 0.88 (t, J=7.33 Hz, 3H) 1.21-1.34 (m, 2H) 1.26 (s, 6H) 1.40-1.54 (m, 2H) 2.55-2.71 (m, 2H) 3.65 (s, 3H) 4.05 (d, J=10.36 Hz, 1H) 4.15 (d, J=10.36 Hz, 1H) 7.32 (d, J=9.09 Hz, 1H) 7.68 (s, 1H) 7.72 (d, J=2.78 Hz, 1H) 7.80 (t, J=7.71 Hz, 1H) 7.93-8.01 (m, 2H) 8.27 (d, J=7.83 Hz, 1H) 8.30 (s, 1H) 8.58 (s, 2H) 10.58 (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 products were isolated by preparative HPLC
  6. additionProduct containing fractions
  7. concentrationconcentrated in a vacuum centrifuge to one fourth of the original volume
  8. extractionthe product was extracted with dichloromethane
  9. customthe extract was evaporated to dryness
  10. customevaporated to dryness
  11. dissolutionThe residue was dissolved in water

Sources & evidence

ORD record
ord-c8f70f1343d54aacb773d0b11523a0a2
Source dataset
uspto-grants-2012_04
Patent number
US08148418B2

Reaction notes

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