4-Methylmorpholine → HCID 57906441, compound

HRID 420545Notes

Reaction equation

HRID 420545 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:23]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[CH:24][N:25]=[C:11]2[CH:10]=1)(C)(C)C.[CH:33]1([C:37](O)=[O:38])CCC1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[NH2:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:23]([N:26]3[CH2:27][CH2:28][N:29]([C:37](=[O:38])[CH3:33])[CH2:30][CH2:31]3)=[CH:24][N:25]=[C:11]2[CH:10]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 19494Cyclobutanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57906493HCID 57906493, compound

Product 1

HCID 57906441HCID 57906441, compoundYield 48.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of [6-(2,4-dichloro-phenyl)-3-piperazin-1-yl-imidazo[1,2-a]pyridin-7-ylmethyl]-carbamic acid tert-butyl ester (30 mg, 0.06 mmol, prepared according to Example 38, Step 23.1), cyclobutanecarboxylic acid (0.007 mL, 0.07 mmol) and NMM (0.035 mL, 0.32 mmol) in DMF (0.5 mL) was added HATU (35.9 mg, 0.095 mmol). The reaction mixture was stirred at RT for 14 h, then poured into AcOEt (20 mL) and washed with a 2.0 M aqueous Na2CO3 solution (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The remaining residue was dissolved in DCM (2 mL) and TFA (1 mL) and the solution was stirred at RT for 30 min. The reaction mixture was concentrated to dryness and the remaining residue purified by reverse phase prep-HPLC (Waters system) to give the title compound (2TFA salt, 20 mg, 0.029 mmol, 46% for 2 steps). MS: 459 [M+1]+; HPLC: AtRet=1.29.

Workup

  1. washwashed with a 2.0 M aqueous Na2CO3 solution (10 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. dissolutionThe remaining residue was dissolved in DCM (2 mL)
  6. stirringTFA (1 mL) and the solution was stirred at RT for 30 min
  7. concentrationThe reaction mixture was concentrated to dryness
  8. customthe remaining residue purified by reverse phase prep-HPLC (Waters system)

Sources & evidence

ORD record
ord-fd5cfba576d941a2bc74cc224e41626c
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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