1,2-Dichloroethane → 4-(Isopropylamino)-2-(methylthio)pyrimidine-5-carboxamide

HRID 2280776Notes

Reaction equation

HRID 2280776 reaction equation
[CH:1]([NH:4][C:5]1[C:10]([C:11](O)=[O:12])=[CH:9][N:8]=[C:7]([S:14][CH3:15])[N:6]=1)([CH3:3])[CH3:2].C1C=CC2N(O)N=[N:22]C=2C=1.C(Cl)CCl.[OH-].[NH4+]>C1COCC1.C(#N)C>[CH:1]([NH:4][C:5]1[C:10]([C:11]([NH2:22])=[O:12])=[CH:9][N:8]=[C:7]([S:14][CH3:15])[N:6]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 127840854-(Isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic Acid

Product 1

HCID 709813214-(Isopropylamino)-2-(methylthio)pyrimidine-5-carboxamideYield 95.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (180 g, 0.792 mol) and HOBt (123 g, 0.911 mol) in anhydrous THF (6.9 L) was added drop-wise a mixture of EDC (174.6 g, 0.911 mol) in acetonitrile (3.7 L) at ambient temperature. The mixture was stirred for 1 h at ambient temperature and then an aqueous ammonium hydroxide solution (989 mL, 28-30% concentrated, 10 eq) was added drop-wise over 30 min. The resulting mixture was heated to gentle reflux for 3 h and then concentrated under reduced pressure. The remaining residue was diluted with a saturated aqueous sodium bicarbonate solution (5 L) and then extracted twice with ethyl acetate (9 L, and 2 L respectively). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (4 water (4 dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 4-(isopropylamino)-2-(methylthio)-pyrimidine-5-carboxamide (171.2 g, 95.5% yield) as a solid. MS (ESI) m/z 227.4 [MA-1]+.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto gentle reflux for 3 h
  3. concentrationconcentrated under reduced pressure
  4. additionThe remaining residue was diluted with a saturated aqueous sodium bicarbonate solution (5 L)
  5. extractionextracted twice with ethyl acetate (9 L, and 2 L respectively)
  6. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (4 water (4
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a382c2df195f4ff3afde529586a3f5d5
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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