Morpholine → HCID 59244360, compound

HRID 912162Notes

Reaction equation

HRID 912162 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[CH:13][C:12]([C:15]3[C:16]4[CH2:29][CH2:28][N:27]([C:30]5[CH:38]=[CH:37][C:33]([C:34]([OH:36])=O)=[CH:32][C:31]=5[F:39])[C:17]=4[N:18]=[C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:20]=3)=[CH:11][N:10]=2)=CC=1.C1C=CC2N(O)N=NC=2C=1.[NH:61]1[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1>ClCCl>[NH2:8][C:9]1[N:10]=[CH:11][C:12]([C:15]2[C:16]3[CH2:29][CH2:28][N:27]([C:30]4[CH:38]=[CH:37][C:33]([C:34]([N:61]5[CH2:66][CH2:65][O:64][CH2:63][CH2:62]5)=[O:36])=[CH:32][C:31]=4[F:39])[C:17]=3[N:18]=[C:19]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[N:20]=2)=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 592443954-(4-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-fluoro-benzoic acid

Product 1

HCID 59244360HCID 59244360, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-fluoro-benzoic acid (120 mg, 0.177 mmol) obtained in Step A in 1-D-21, WSCI (68 mg, 0.35 mmol), HOBt (24 mg, 0.15 mmol) and morpholine (31 μl, 0.35 mmol), dichloromethane (4 ml) was added, followed by stirring for 1 hour. The reaction mixture was washed with water, and subsequently dried over sodium sulfate. The drying agent was removed, followed by concentration and drying. To this, TFA (2 ml) was added, followed by stirring at 80° C. for 4 hours. After TFA was removed under reduced pressure, dichloromethane was added, followed by washing with aqueous sodium hydrogencarbonate solution. The organic layer was dried over sodium sulfate, filtered and concentrated, to obtain a crude product. Purification by silica gel column chromatography (dichloromethane/methanol=10/1) afforded {4-[4-(2-amino-pyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl]-3-fluoro-phenyl}-morpholin-4-yl-methanone as a colorless solid (86 mg, 96%).

Workup

  1. washThe reaction mixture was washed with water
  2. dry with materialsubsequently dried over sodium sulfate
  3. customThe drying agent was removed
  4. concentrationfollowed by concentration
  5. customdrying
  6. additionTo this, TFA (2 ml) was added
  7. stirringby stirring at 80° C. for 4 hours
  8. customAfter TFA was removed under reduced pressure, dichloromethane
  9. additionwas added
  10. washby washing with aqueous sodium hydrogencarbonate solution
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto obtain a crude product
  15. customPurification by silica gel column chromatography (dichloromethane/methanol=10/1)

Sources & evidence

ORD record
ord-1af509f4d1ff49069eea33f252771713
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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