Formaldehyde → HCID 69284565, compound

HRID 2225255Notes

Reaction equation

HRID 2225255 reaction equation
F[C:2](F)(F)[C:3](O)=O.N[C@@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16](=[O:31])[CH2:17][NH:18][C:19](=[O:30])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=2)[C@H:11]([CH2:32][O:33][C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH2:10]1.[C:40]([BH3-])#[N:41].[Na+].[CH2:44]=O>CO.CC(C)=O>[CH:2]([N:41]([CH3:40])[C@@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16](=[O:31])[CH2:17][NH:18][C:19](=[O:30])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:27])([F:28])[F:29])[CH:21]=2)[C@H:11]([CH2:32][O:33][C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH2:10]1)([CH3:3])[CH3:44]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 69285485HCID 69285485, compound

Product 1

HCID 69284565HCID 69284565, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

The sample of the trifluoroacetic acid salt of N-(2-((1S,2R,4R)-4-amino-2-((pyridin-3-yloxy)methyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide prepared in Example 5c, Step 2 was dissolved in methanol (3 mL) and treated sequentially with acetone (ca. 1 mL) and sodium cyanoborohydride (28 mg). The mixture was stirred at rt for 3 h. Aqueous formaldehyde (ca. 1 mL) was added and the mixture was stirred at rt for 3 days. The mixture was concentrated under vacuum and the residue was taken up in ethyl acetate and saturated aqueous NaHCO3. The phases were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over Na2SO4 and concentrated. Purification by reverse phase HPLC and lyophilization provided the bis-trifluoroacetic acid salt of the title product, N-(2-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((pyridin-3-yloxy)methyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide, as a white powder (10 mg). MS found: (M+H)+=507.2.

Workup

  1. stirringthe mixture was stirred at rt for 3 days
  2. concentrationThe mixture was concentrated under vacuum
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC and lyophilization

Sources & evidence

ORD record
ord-3929c657f58140e081a2ed9ba471698f
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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