1,2-Dichloroethane → 4-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(methylthio)pyrimidine-5-carboxamide

HRID 2280781Notes

Reaction equation

HRID 2280781 reaction equation
[C:1]12([NH:6][C:7]3[C:12]([C:13](O)=[O:14])=[CH:11][N:10]=[C:9]([S:16][CH3:17])[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.C1C=CC2N(O)N=[N:24]C=2C=1.C(Cl)CCl.[OH-].[NH4+]>C1COCC1.C(#N)C>[C:1]12([NH:6][C:7]3[C:12]([C:13]([NH2:24])=[O:14])=[CH:11][N:10]=[C:9]([S:16][CH3:17])[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 709813424-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(methylthio)pyrimidine-5-carboxylic acid

Product 1

HCID 709820104-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(methylthio)pyrimidine-5-carboxamideYield 93%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 4-(bicyclo[1.1.1]pentan-1-ylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (108 g, 0.43 mol) and HOBt (67 g, 0.49 mol) in anhydrous THF (4 L) was added drop-wise a mixture of EDC (94 g, 0.49 mol) in acetonitrile (2 L) at room temperature. After the reaction mixture was stirred for 1 hr at room temperature, aqueous ammonium hydroxide (600 mL, 28-30% concentrated, 10 eq) was added drop-wise over 30 min and then the mixture was heated to gentle reflux for 3 h (60±5° C.). After that all solvents were removed under reduced pressure, the residual paste/solid was diluted with saturated aqueous sodium bicarbonate solution (2 L) and the resulting suspension was filtered to afford the desired compound (100 g, 0.4 mol, 93% yield) as an off-white fluffy solid; MS (ESI): m/z 251.1 [M+1]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto gentle reflux for 3 h (60±5° C.)
  3. customAfter that all solvents were removed under reduced pressure
  4. additionthe residual paste/solid was diluted with saturated aqueous sodium bicarbonate solution (2 L)
  5. filtrationthe resulting suspension was filtered

Sources & evidence

ORD record
ord-369a0dd2734742899d7b7acc951606a3
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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