4-Methylmorpholine → 8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

HRID 558958Notes

Reaction equation

HRID 558958 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]([C:17](=[O:40])[NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([N:28]3[CH2:34][CH2:33][CH2:32][CH2:31][C:30]4[CH:35]=[CH:36][CH:37]=[CH:38][C:29]3=4)=[O:27])=[CH:22][C:21]=1[CH3:39])[CH2:5][C:6](=[O:16])[N:7]2[CH2:12][C:13](O)=[O:14].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+].[Cl-].[NH4+]>C1COCC1.O>[CH3:39][C:21]1[CH:22]=[C:23]([C:26]([N:28]2[CH2:34][CH2:33][CH2:32][CH2:31][C:30]3[CH:35]=[CH:36][CH:37]=[CH:38][C:29]2=3)=[O:27])[CH:24]=[CH:25][C:20]=1[CH2:19][NH:18][C:17]([N:4]1[C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[F:1])[N:7]([CH2:12][CH2:13][OH:14])[C:6](=[O:16])[CH2:5]1)=[O:40]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 11570214{5-Fluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid

Product 1

HCID 115482588-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {5-fluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid from Example 8 (70 mg, 0.13 mmol) in THF (4.0 ml) was added N-methylmorpholine (18 μl, 0.18 mmol. The solution was cooled in an ice/water bath and isobutyl chloroformate (23 μl, 0.18 mmol) was added. The mixture was stirred in the ice/water bath for 1 h, filtered and added to a solution of sodium borohydride (12 mg, 0.32 mmol) in water (1.0 ml) in an ice/water bath. The mixture was allowed to warm to room temperature slowly and stirred at room temperature for 1 h. Saturated ammonium chloride (1 ml) was added and the mixture was evaporated in vacuo. The residue was taken up in water and extracted with chloroform. The organic phase was washed with brine, dried and evaporated in vacuo to give a white solid; yield 56 mg, 81%.

Workup

  1. temperatureThe solution was cooled in an ice/water bath
  2. filtrationfiltered
  3. customthe mixture was evaporated in vacuo
  4. extractionextracted with chloroform
  5. washThe organic phase was washed with brine
  6. customdried
  7. customevaporated in vacuo
  8. customto give a white solid

Sources & evidence

ORD record
ord-dfb2ed4e855c405e9b4af0af4838eaaa
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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