Dichloromethane → HCID 9806212, compound

HRID 1740868Notes

Reaction equation

HRID 1740868 reaction equation
C(O[C:6]([N:8]1[CH2:13][C:12](=[O:14])[N:11]([CH2:15][C:16]([F:19])([F:18])[F:17])[CH2:10][C@@H:9]1[CH2:20][CH2:21][CH2:22][CH3:23])=O)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:38]([C:40]1[CH:53]=[CH:52][C:43]([CH2:44][N:45]2[C:49](C=O)=[CH:48][N:47]=[CH:46]2)=[CH:42][CH:41]=1)#[N:39].C(=O)(O)[O-].[Na+].C(Cl)[Cl:60]>FC(F)(F)C(O)=O>[ClH:60].[ClH:60].[CH2:20]([C@H:9]1[CH2:10][N:11]([CH2:15][C:16]([F:17])([F:18])[F:19])[C:12](=[O:14])[CH2:13][N:8]1[CH2:6][C:49]1[N:45]([CH2:44][C:43]2[CH:52]=[CH:53][C:40]([C:38]#[N:39])=[CH:41][CH:42]=2)[CH:46]=[N:47][CH:48]=1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 106322894-[(5-Formylimidazol-1-yl)methyl]benzonitrileHCID 67597500HCID 67597500, compound

Product 1

HCID 9806212HCID 9806212, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
20 °C

Procedure

A solution of the product from Step D (0.578 g, 1.71 mmol) was stirred in 30% trifluoroacetic acid in methylene chloride for 1 h. The volatiles were removed in vacuo, and the residue dissolved in dichloroethane (5 mL). The pH was adjusted to 5-6 with N-methylmorpholine. Sodium triacetoxyborohydride (0.544 g, 2.57 mmol) and 1-(4-cyanobenzyl)imidazolyl-5-carboxaldehyde from Step I (0.361 g, 1.71 mmol) was added. The reaction was stirred overnight at 20° C. then poured into saturated sodium bicarbonate solution. The organic phase was washed with saturated brine and dried over magnesium sulfate. The crude product was purified by preparative HPLC on a 40×100 mm Waters PrepPak® reverse phase HPLC column (Delta-Pak™ C18 15 μm, 100 Å) using a gradient elution of 25% (0.1% TFA in acetonitrile), 75% (0.1% TFA in water) progressing to 45% (0.1% TFA in acetonitrile), 55% (0.1% TFA in water) over 50 min. Pure fractions were combined, concentrated, and the residue partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was dried over magnesium sulfate. The purified product was converted to the hydrochloride salt with HCl in dichloromethane. The title compound was obtained as a white solid. FAB ms (m+1) 434. Anal. Calc. for C22H26F3N5O·2.0 HCl: C, 52.18; H, 5.57; N, 13.83. Found: C, 52.41; H, 5.60; N, 13.65.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue dissolved in dichloroethane (5 mL)
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was purified by preparative HPLC on a 40×100 mm Waters PrepPak® reverse phase HPLC column (Delta-Pak™ C18 15 μm, 100 Å)
  6. washa gradient elution of 25% (0.1% TFA in acetonitrile), 75% (0.1% TFA in water) progressing to 45% (0.1% TFA in acetonitrile), 55% (0.1% TFA in water) over 50 min
  7. concentrationconcentrated
  8. customthe residue partitioned between ethyl acetate and saturated sodium bicarbonate solution
  9. dry with materialThe organic layer was dried over magnesium sulfate

Sources & evidence

ORD record
ord-723e1eb812d147cc9e7a33fe5e0c41bc
Source dataset
uspto-grants-1999_10
Patent number
US05972942

Reaction notes

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