1,2-Dichloroethane → 5-Fluoro-2-{[(1-{[(1R,2R)-2-phenylcyclopropyl]carbonyl}piperidin-4-yl)methyl]amino}pyrimidine

HRID 1351593Notes

Reaction equation

HRID 1351593 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:6][CH:7]=1.[C:16]1([C@@H:22]2[CH2:24][C@H:23]2[C:25](O)=[O:26])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:25]([C@@H:23]3[CH2:24][C@H:22]3[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:26])[CH2:12][CH2:11]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 22135716HCID 22135716, compound

Product 1

HCID 586353495-Fluoro-2-{[(1-{[(1R,2R)-2-phenylcyclopropyl]carbonyl}piperidin-4-yl)methyl]amino}pyrimidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-fluoro-N-(piperidin-4-ylmethyl)pyrimidin-2-amine (1.00 g, 4.76 mmol), (1R,2R)-2-phenylcyclopropanecarboxylic acid (T. Riley et al., J. Med. Chem., 15, 1187, 1972) (0.77 g, 4.76 mmol), EDC (1.37 g, 7.13 mmol) and HOBt (0.96 g, 7.13 mmol) in DMF (10 mL) was stirred at rt for 2 h. The reaction mixture was diluted with ethyl acetate (200 mL), washed with aqueous saturated NaHCO3 (50 mL), water (5×50 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel 60 (90 g), eluting with 10:1–15:89–75 CH2Cl2:2-propanol:hexane to give the title compound. M.S. (M+1): 355.

Workup

  1. washwashed with aqueous saturated NaHCO3 (50 mL), water (5×50 mL), brine (20 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel 60 (90 g)
  6. washeluting with 10:1–15:89–75 CH2Cl2

Sources & evidence

ORD record
ord-bc02db0a36414b489b21b0c2ee255343
Source dataset
uspto-grants-2007_05
Patent number
US07217716B2

Reaction notes

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