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

HRID 1351595Notes

Reaction equation

HRID 1351595 reaction equation
[CH3:1][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>[CH3:1][C:2]1[CH:7]=[N:6][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:4][CH:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 221355685-methyl-N-(4-piperidinylmethyl)-2-Pyrimidinamine

Product 1

HCID 586353355-methyl-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-methyl-N-(piperidin-4-ylmethyl)pyrimidin-2-amine (5.00 g, 0.024 mol), (1R,2R)-2-phenylcyclopropanecarboxylic acid (T. Riley et al., J. Med. Chem., (1972), 15, 1187) (3.93 g, 0.024 mol), EDC (6.97 g, 0.036 mol) and HOBt (4.91 g, 0.036 mol) in DMF (50 mL) was stirred at RT for 2 h. The reaction mixture was diluted with ethyl acetate (400 mL), washed with aqueous saturated NaHCO3 (100 mL), water (5×100 mL), brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel 60 (400 g), eluting with 50–100% ethyl acetate in hexane to give 5-methyl-2-{[(1-{[(1R,2R)-2-phenylcyclopropyl]carbonyl}piperidin-4-yl)methyl]amino}pyrimidine. M.S. (M+1): 351.

Workup

  1. washwashed with aqueous saturated NaHCO3 (100 mL), water (5×100 mL), brine (50 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel 60 (400 g)
  6. washeluting with 50–100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-50aaf12d7f154d2182a8a4e96b3dacf3
Source dataset
uspto-grants-2007_05
Patent number
US07217716B2

Reaction notes

Loading…