Morpholine → HCID 21262659, compound

HRID 567752Notes

Reaction equation

HRID 567752 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:14]=[C:13]([CH:15]=O)[NH:12][C:8]=2[N:9]=[CH:10][N:11]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CO.CN1C(=O)N(C)CCC1.C(O)(=O)C.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:14]=[C:13]([CH2:15][N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[NH:12][C:8]=2[N:9]=[CH:10][N:11]=1

Participants

7

Reactant 2

HCID 8083MorpholineHCID 110976994-(3-chloroanilino)-6-formyl-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 21262659HCID 21262659, compound

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

109 mg (0.40 mmol) of 4-(3-chloroanilino)-6-formyl-7H-pyrrolo[2,3-d]pyrimidine (stage 1.6) and 70 μl (0.8 mmol) of morpholine in 6 ml of methanol, 2 ml of DMPU and 50 μl of acetic acid are heated at 50° C. for 2 h. 30 mg of Raney nickel are then added and the mixture is hydrogenated at 50° C. The catalyst is filtered off, the filtrate is evaporated and the residue is dissolved in ethyl acetate and satd Na2CO3 solution. The aqueous phase separated off is extracted twice with ethyl acetate; the organic phases are washed with satd NaHCO3 solution, twice with water and brine, dried (MgSO4) and evaporated. The residue is taken up in methanol, and the solution is treated with silica gel and dried. The powder is added to a silica gel column and eluted with CH2Cl2/methanol=10:1. Crystallization from ethyl acetate/diethyl ether/hexane yields 4-(3-chloroanilino)-6-[(morpholin-4-yl)-methyl]-7H-pyrrolo[2,3-d]pyrimidine; m.p: 244-246° C.; HPLC: tRet(Grad20)=7.4; TLC-Rf=0.20 (CH2Cl2/methanol 10:1); FAB-MS: (M+H)+=344.

Workup

  1. customis hydrogenated at 50° C
  2. filtrationThe catalyst is filtered off
  3. customthe filtrate is evaporated
  4. dissolutionthe residue is dissolved in ethyl acetate
  5. customThe aqueous phase separated off
  6. extractionis extracted twice with ethyl acetate
  7. washthe organic phases are washed with satd NaHCO3 solution, twice with water and brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. additionthe solution is treated with silica gel
  11. customdried
  12. additionThe powder is added to a silica gel column
  13. washeluted with CH2Cl2/methanol=10:1
  14. customCrystallization from ethyl acetate/diethyl ether/hexane

Sources & evidence

ORD record
ord-f8fc9d248ab648e5b12eeb393a9569be
Source dataset
uspto-grants-2001_01
Patent number
US06180636B2

Reaction notes

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