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

HRID 1827233Notes

Reaction equation

HRID 1827233 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-57943a0886fc4ea8aea8c887148b914f
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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