Diisopropylethylamine → HCID 67515210, compound

HRID 473917Notes

Reaction equation

HRID 473917 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][N:14]([C:18](OC(C)(C)C)=[O:19])[CH2:13][C:12]=3[CH:25]=2)=[CH:4][C:3]=1[N+:26]([O-:28])=[O:27].CCN(C(C)C)C(C)C.[OH:38][C:39]1([C:50]([F:53])([F:52])[F:51])[CH2:45][CH:44]2[N:46](C(Cl)=O)[CH:41]([CH2:42][CH2:43]2)[CH2:40]1>C1COCC1.CN1C(=O)CCC1>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][N:14]([C:18]([N:46]4[CH:44]5[CH2:43][CH2:42][CH:41]4[CH2:40][C:39]([C:50]([F:51])([F:52])[F:53])([OH:38])[CH2:45]5)=[O:19])[CH2:13][C:12]=3[CH:25]=2)=[CH:4][C:3]=1[N+:26]([O-:28])=[O:27]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 668202001,1-dimethylethyl 7-(6-amino-5-nitropyridin-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateHCID 86672038HCID 86672038, compound

Product 1

HCID 67515210HCID 67515210, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1,1-dimethylethyl 7-(6-amino-5-nitropyridin-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (1.1 g, 3.1 mmol) and DIPEA (2.7 mL, 16 mmol) in THF (10 mL) and NMP (5 mL) was added 3-hydroxy-3-(trifluoromethyl)-8-azabicyclo[3.2.1]octane-8-carbonyl chloride (reagent preparation 37, 0.81 g, 3.1 mmol). The reaction mixture was heated (50° C.) for four hours and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography provided 8-{[7-(6-amino-5-nitropyridin-3-yl)-2,3-dihydro-1,4-benzoxazepin-4 (5H)-yl]carbonyl}-3-(trifluoromethyl)-8-azabicyclo[3.2.1]octan-3-ol (1.1 g, 69% yield) as red oil. MS (ES) for C23H24F3N5O5: 507.2 (MH+).

Workup

  1. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-d828aed2000f474eb84016979d98b871
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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