Morpholine → N2-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-ylcarbonyl)-5-nitropyrimidine-2,4-diamine

HRID 450389Notes

Reaction equation

HRID 450389 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:11]2[N:16]=[C:15]([C:17](O)=[O:18])[C:14]([N+:20]([O-:22])=[O:21])=[C:13]([NH:23][C:24]3[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=3)[N:12]=2)[CH3:9])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:63]1[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1>CN(C=O)C.O.CCOC(C)=O>[F:1][C:2]1[CH:7]=[N:6][C:5]([C@@H:8]([NH:10][C:11]2[N:12]=[C:13]([NH:23][C:24]3[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=3)[C:14]([N+:20]([O-:22])=[O:21])=[C:15]([C:17]([N:63]3[CH2:68][CH2:67][O:66][CH2:65][CH2:64]3)=[O:18])[N:16]=2)[CH3:9])=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 687821322-{[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylic acid2×

Product 1

HCID 68780089N2-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-ylcarbonyl)-5-nitropyrimidine-2,4-diamine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]-5-nitropyrimidine-4-carboxylic acid (Intermediate 50, 406 mg, ˜1 mmol), in DMF (5 ml) were added DIPEA (˜0.3 ml), HATU (456 mg) and morpholine (0.130 ml) at ambient temperature. The resulting mixture was stirred overnight. The mixture was diluted with H2O and EtOAc and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution, dried and evaporation of the volatiles under reduced pressure gave a colored residue. Purification by column chromatography (ISCO, 50%→70% EtOAc/hexanes) gave the title compound. LCMS: 473 [M+1].

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. washThe combined organic layers were washed with brine, saturated NaHCO3 (aq) solution
  3. customdried
  4. customevaporation of the volatiles under reduced pressure
  5. customgave a colored residue
  6. customPurification by column chromatography (ISCO, 50%→70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fd56a3750acf4dab85bddc9c2d98fc05
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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