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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 450389
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HRID 450389 반응식
[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
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참가 물질

8

반응물 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 acid2회

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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].

후처리

  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)

출처 및 근거

ORD 기록
ord-fd56a3750acf4dab85bddc9c2d98fc05
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08486966B2

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