Morpholine → (1-(5-(2-Fluoro-5-(1-hydroxyethyl)phenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

HRID 630530Notes

Reaction equation

HRID 630530 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[F:40][C:41]1[CH:46]=[CH:45][C:44]([CH:47]([OH:49])[CH3:48])=[CH:43][C:42]=1[C:50]1[CH:51]=[N:52][C:53]([N:56]2[C:64]3[C:59](=[CH:60][CH:61]=[C:62]([C:65](O)=[O:66])[CH:63]=3)[C:58]([S:68][CH3:69])=[CH:57]2)=[N:54][CH:55]=1>CN(C=O)C>[F:40][C:41]1[CH:46]=[CH:45][C:44]([CH:47]([OH:49])[CH3:48])=[CH:43][C:42]=1[C:50]1[CH:51]=[N:52][C:53]([N:56]2[C:64]3[C:59](=[CH:60][CH:61]=[C:62]([C:65]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)=[O:66])[CH:63]=3)[C:58]([S:68][CH3:69])=[CH:57]2)=[N:54][CH:55]=1

Participants

6

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 1186663861-(5-(2-Fluoro-5-(1-hydroxyethyl)phenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylic acid

Product 1

HCID 118666108(1-(5-(2-Fluoro-5-(1-hydroxyethyl)phenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.38 g, 0.99 mmol), diisopropylethylamine (0.41 mL, 2.48 mmol) and morpholine (0.08 mL, 0.99 mmol) were added at 0° C. to a solution of 300b) (0.35, 0.83 mmol) in dry DMF (2 mL). The reaction mixture was stirred at room temperature for 6 h and then quenched with ice-cold water. The mixture was extracted with dichloromethane (2×50 mL), the combined organic layers were dried over sodium sulfate and the solvent was removed in vacuo. The remnant was purified by flash column chromatography [silica, dichloromethane with 1.5% methanol]. White solid. Yield: 0.32 g (80% of theory)

Workup

  1. customquenched with ice-cold water
  2. extractionThe mixture was extracted with dichloromethane (2×50 mL)
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. customthe solvent was removed in vacuo
  5. customThe remnant was purified by flash column chromatography [silica, dichloromethane with 1.5% methanol]

Sources & evidence

ORD record
ord-ff5b6251026847c6a72bedb6742727da
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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