Isobutyl chloroformate → HCID 131727831, compound

HRID 1869587Notes

Reaction equation

HRID 1869587 reaction equation
Cl.[Cl:2][C:3]1[C:4]([N:35]2[CH2:40][CH2:39][CH:38]([C:41]([OH:43])=O)[CH2:37][CH2:36]2)=[N:5][CH:6]=[C:7]([C:9](=[O:34])[NH:10][C:11]2[S:12][C:13]([N:22]3[CH2:27][CH2:26][N:25]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)[CH2:24][CH2:23]3)=[C:14]([C:16]3[S:17][CH:18]=[C:19]([Cl:21])[CH:20]=3)[N:15]=2)[CH:8]=1.ClC(OC[CH:49]([CH3:51])[CH3:50])=O.[CH3:52][S:53]([NH2:56])(=[O:55])=[O:54].C([O-])(O)=O.[Na+]>C1COCC1.CN1CCOCC1.C1CCN2C(=NCCC2)CC1>[ClH:2].[Cl:2][C:3]1[C:4]([N:35]2[CH2:36][CH2:37][CH:38]([C:41]([NH:10][CH2:9][CH2:7][CH2:6][N:5]3[CH:51]=[CH:49][CH:50]=[CH:8][CH2:3][C:4]3=[N:56][S:53]([CH3:52])(=[O:55])=[O:54])=[O:43])[CH2:39][CH2:40]2)=[N:5][CH:6]=[C:7]([CH:8]=1)[C:9]([NH:10][C:11]1[S:12][C:13]([N:22]2[CH2:23][CH2:24][N:25]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH2:26][CH2:27]2)=[C:14]([C:16]2[S:17][CH:18]=[C:19]([Cl:21])[CH:20]=2)[N:15]=1)=[O:34]

Participants

8

Reactant 4

HCID 62365Isobutyl chloroformateHCID 72879MethanesulfonamideHCID 516892Sodium BicarbonateHCID 87588882HCID 87588882, compound

Product 1

HCID 131727831HCID 131727831, compound

Reagents, catalysts & solvents 3

HCID 79724-MethylmorpholineSolventHCID 8028TetrahydrofuranSolvent2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneSolvent

Procedure

To a solution of 300 mg of the compound of Example 16 in 6 ml of THF, 56 μl of N-methylmorpholine were added, 60 μl of isobutyl chloroformate was added at −15° C., and the mixture was stirred for 1.5 hours. And, to a solution of 96 mg of methanesulfonamide in 4 ml of THF, 348 μl of 1,8-diazabicyclo[5,4,0]-7-undecene was added, and the mixture was stirred at room temperature for 19 hours and at 50° C. for 2 days. The reaction solution was mixed with saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was washed with brine and dried over sodium sulfate. The residue obtained by the evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (hexane-THF=2:1˜0:1) and then by silica gel column chromatography (chloroform-MeOH=100:0˜100:3), and the obtained compound was dissolved in chloroform-EtOH. A 0.1M HCl-EtOAc solution was added thereto, the solvent was evaporated under reduced pressure, EtOH-diethylether was added thereto, and the thus-produced precipitate was collected by filtration to obtain 30 mg of 5-chloro-N-[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]-6-(4-(3-[2-(methanesulfonylimino)azepin-1-yl]propylaminocarbonyl)piperidin-1-yl)nicotinamide hydrochloride.

Workup

  1. stirringthe mixture was stirred at room temperature for 19 hours and at 50° C. for 2 days
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe residue obtained by the evaporation of the solvent under reduced pressure
  6. customwas purified by silica gel column chromatography (hexane-THF=2:1˜0:1)
  7. dissolutionby silica gel column chromatography (chloroform-MeOH=100:0˜100:3), and the obtained compound was dissolved in chloroform-EtOH
  8. additionA 0.1M HCl-EtOAc solution was added
  9. customthe solvent was evaporated under reduced pressure, EtOH-diethylether
  10. additionwas added
  11. filtrationthe thus-produced precipitate was collected by filtration

Sources & evidence

ORD record
ord-e57df0bbbb2a4542a7b360b80040456a
Source dataset
uspto-grants-2009_12
Patent number
US07638536B2

Reaction notes

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