Diisopropylethylamine → 5-Pyrimidinecarboxamide, 4-amino-2-(ethylthio)-N-methoxy-N-methyl-

HRID 1435167Notes

Reaction equation

HRID 1435167 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([S:11][CH2:12][CH3:13])[N:3]=1.F[P-](F)(F)(F)(F)F.[N:21]1([O:30][C:31](N(C)C)=[N+](C)C)[C:25]2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C.O>[CH3:31][O:30][N:21]([CH3:25])[C:8]([C:7]1[C:2]([NH2:1])=[N:3][C:4]([S:11][CH2:12][CH3:13])=[N:5][CH:6]=1)=[O:10]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2753004-Amino-2-(ethylthio)pyrimidine-5-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 119748325-Pyrimidinecarboxamide, 4-amino-2-(ethylthio)-N-methoxy-N-methyl-Yield 98%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-amino-2-ethylsulfanyl-pyrimidine-5-carboxylic acid (1.00 g, 5.40 mmol, Sigma) in dimethylformamide were added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (3.06 g, 8.1 mmol, Aldrich), 1-hydroxy-benzotriazole hydrate (1.09 g, 8.1 mmol, Aldrich) followed by diisopropylethylamine (3.94 g, 29.7 mmol) at 0° C. After stirring for 10-15 minutes, N,O-dimethyl-hydroxylamine. HCl (790 mg, 8.1 mmol, Aldrich) was added. The reaction was stirred at 0° C. to room temperature for 2 hours and then diluted with ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried and concentrated. The crude product was purified on silica gel with 1:1 hexane/ethyl acetate to give 4-amino-2-ethylsulfanyl-pyrimidine-5-carboxylic acid methoxy-methyl-amide as a white solid (1.189 g, 98% yield). HRMS, observed: 242.0836; Calcd for M+: 242.0837

Workup

  1. stirringThe reaction was stirred at 0° C. to room temperature for 2 hours
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe crude product was purified on silica gel with 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-96054699ef8541609acd2f8fe39a5820
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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