4-Methylmorpholine → HCID 90370084, compound

HRID 2176047Notes

Reaction equation

HRID 2176047 reaction equation
[CH3:1][O:2][C:3](=[O:51])[C:4]([CH3:50])([CH3:49])[CH2:5][CH2:6][C:7]([N:9]([CH2:15][C:16]1[CH:17]=[C:18]([CH:46]=[CH:47][CH:48]=1)[C:19]([NH:21][C:22]1[S:23][C:24]2[CH2:45][CH2:44][CH2:43][CH2:42][C:25]=2[C:26]=1[C:27]([NH:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]([CH3:41])([CH3:40])[C:37](O)=[O:38])=[N:34][CH:35]=1)=[O:28])=[O:20])[CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[O:8].CN1CCOCC1.ClC(OCC(C)C)=O>C1COCC1>[OH:38][CH2:37][C:36]([C:33]1[N:34]=[CH:35][C:30]([NH:29][C:27]([C:26]2[C:25]3[CH2:42][CH2:43][CH2:44][CH2:45][C:24]=3[S:23][C:22]=2[NH:21][C:19]([C:18]2[CH:17]=[C:16]([CH:48]=[CH:47][CH:46]=2)[CH2:15][N:9]([CH:10]([CH2:11][CH3:12])[CH2:13][CH3:14])[C:7](=[O:8])[CH2:6][CH2:5][C:4]([CH3:50])([CH3:49])[C:3]([O:2][CH3:1])=[O:51])=[O:20])=[O:28])=[CH:31][CH:32]=1)([CH3:40])[CH3:41]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 90370190HCID 90370190, compound

Product 1

HCID 90370084HCID 90370084, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 410 mg of 2-{5-[({2-[(3-{[(5-methoxy-4,4-dimethyl-5-oxopentanoyl)(pentan-3-yl)amino]methyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]pyridin-2-yl}-2-methylpropanoic acid, 75 mg of 4-methylmorpholine and 10 mL of THF was added 0.089 mL of isobutyl chloroformate under ice cooling, followed by stirring for 10 minutes at room temperature. The reaction mixture was filtered, and then the filtrate was cooled with ice. 65 mg of sodium borohydride and 1.0 mL of water were added thereto, followed by stirring for 10 minutes at room temperature. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2), thereby obtaining 155 mg of methyl 5-[{3-[(3-{[6-(1-hydroxy-2-methylpropan-2-yl)pyridin-3-yl]carbamoyl}-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)carbamoyl]benzyl}(pentan-3-yl)amino]-2,2-dimethyl-5-oxopentanoate.

Workup

  1. filtrationThe reaction mixture was filtered
  2. temperaturethe filtrate was cooled with ice
  3. addition65 mg of sodium borohydride and 1.0 mL of water were added
  4. stirringby stirring for 10 minutes at room temperature
  5. additionA saturated aqueous ammonium chloride solution was added to the reaction mixture
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-2bd97ed4cd504edcb64b6fdbcc5c216d
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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