Propanal → HCID 24890718, compound

HRID 1507080Notes

Reaction equation

HRID 1507080 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][CH3:49].C(Cl)(=O)C>C1COCC1.CO>[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]([CH3:46])([NH:15][CH2:47][CH2:48][CH3:49])[CH3:45]

Participants

7

Reactant 4

HCID 527PropanalHCID 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 24890718HCID 24890718, compoundYield 51.3%

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 propionaldehyde (6.7 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 (30 mg, 48%) as the hydrochloride salt. LCMS m/z (%)=511.4 (M+H, 37Cl 60.5), 509.3 (M+H, 35Cl 100.0%). 1H NMR (400 MHz, DMSO-d6) δ 0.87 (t, J=7.45 Hz, 3H) 1.26 (s, 6H) 1.46-1.58 (m, 2H) 2.53-2.64 (m, 2H) 3.65 (s, 3H) 4.06 (d, J=10.36 Hz, 1H) 4.16 (d, J=10.36 Hz, 1H) 7.33 (d, J=9.09 Hz, 1H) 7.69 (s, 1H) 7.73 (d, J=2.78 Hz, 1H) 7.80 (t, J=7.83 Hz, 1H) 7.94-8.02 (m, 2H) 8.28 (d, J=8.34 Hz, 1H) 8.31 (s, 1H) 8.65 (s, 2H) 10.59 (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-37c9c922d7ba4778b2f23f7706865d7e
Source dataset
uspto-grants-2015_12
Patent number
US09221755B2

Reaction notes

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