1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 58451141, compound

HRID 1361501Notes

Reaction equation

HRID 1361501 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH:16]3[CH:20]([OH:21])[CH2:19][NH:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C1CCN2C(=NCCC2)CC1.Cl[C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([O:44][CH3:45])[CH:42]=2)[N:37]=[CH:36][N:35]=1.ClC1C2C(=CC=C(OC)C=2)N=C(C)N=1>CO.CCOC(C)=O.CCOCC.C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C@@H:16]3[C@@H:20]([OH:21])[CH2:19][N:18]([C:34]4[C:43]5[C:38](=[CH:39][CH:40]=[C:41]([O:44][CH3:45])[CH:42]=5)[N:37]=[CH:36][N:35]=4)[CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 111831744-Chloro-6-methoxyquinazolineHCID 122776024-Chloro-6-methoxy-2-methylquinazolineHCID 66968375(4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone2×

Product 1

HCID 58451141HCID 58451141, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 0.326 mmoles of (4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone (synthesis described above in Example 5), add 1.6 mL acetonitrile and 1.6 mmoles of DBU. The stirred solution was cooled in ice and then 0.358 mmoles of 4-chloro-6-methoxy-quinazoline was added and the reaction mixture was allowed to stir for a period of 2.5 hours. To 0.326 mmoles of (4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone, add 1.6 mL acetonitrile and 1.63 mmoles of DBU. The stirred solution was cooled in ice and then 0.358 mmoles of 4-chloro-6-methoxy-2-methyl-quinazoline (from Step 2 above) was added and the reaction mixture was allowed to stir for a period of 2.5 hours. For the reaction workup, the reaction mixture was diluted with methanol and concentrated on the rotavap. To the concentrate about 30 mL of water was added and was extracted with 40 mL EtOAc. The organic layer was separated and washed with 30 mL of 1M aq K2CO3 solution, and brine, dried over MgSO4 and excess solvent was removed on rotavap to yield a crude oil. This was diluted with about 2 mL EtOAc and about 8 mL ether was added and the white solid obtained was filtered off and vaccum dried to give the title compound in 50% yield. LC-MS: m/z=468 (M++1).

Workup

  1. temperatureThe stirred solution was cooled in ice
  2. temperatureThe stirred solution was cooled in ice
  3. stirringto stir for a period of 2.5 hours
  4. concentrationconcentrated on the rotavap
  5. additionTo the concentrate about 30 mL of water was added
  6. extractionwas extracted with 40 mL EtOAc
  7. customThe organic layer was separated
  8. washwashed with 30 mL of 1M aq K2CO3 solution, and brine
  9. dry with materialdried over MgSO4 and excess solvent
  10. customwas removed on rotavap
  11. customto yield a crude oil
  12. additionwas added
  13. customthe white solid obtained
  14. filtrationwas filtered off
  15. customvaccum dried

Sources & evidence

ORD record
ord-223140f6d18e4ff0a0dbc8a8ac6d7089
Source dataset
uspto-grants-2011_02
Patent number
US07880002B2

Reaction notes

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