4-Methylmorpholine → HCID 74931453, compound

HRID 1095102Notes

Reaction equation

HRID 1095102 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][C:33]2[CH:38]=[CH:37][C:36]([C:39](F)=[O:40])=[CH:35][CH:34]=2)=[C:6]([CH:8]2[C:13]3([C:21]4[C:16](=[CH:17][C:18]([Cl:22])=[CH:19][CH:20]=4)[NH:15][C:14]3=[O:23])[CH:12]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[CH2:11][C:10](=[O:31])[NH:9]2)[CH:7]=1.[NH2:42][C:43]([CH3:47])([CH3:46])[CH2:44][OH:45].CN1CCOCC1>O1CCCC1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][C:33]2[CH:38]=[CH:37][C:36]([C:39](=[O:40])[NH:42][C:43]([CH3:47])([CH3:46])[CH2:44][OH:45])=[CH:35][CH:34]=2)=[C:6]([CH:8]2[C:13]3([C:21]4[C:16](=[CH:17][C:18]([Cl:22])=[CH:19][CH:20]=4)[NH:15][C:14]3=[O:23])[CH:12]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[CH2:11][C:10](=[O:31])[NH:9]2)[CH:7]=1

Participants

7

Reactant 3

HCID 79724-MethylmorpholineHCID 118072-Amino-2-methyl-1-propanolHCID 74931420HCID 74931420, compound

Product 1

HCID 74931453HCID 74931453, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of racemic(2′R, 3R, 4′S)-2′-[5-bromo-2-(4-fluorocarbonyl-phenoxy)-phenyl]-6-chloro-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.18 g, 0.28 mmol) in tetrahydrofuran (20 mL) was added 2-amino-2-methyl-propan-1-ol (0.2 g, 2.24 mmol), N-methylmorpholine (0.2 g, 2 mmol) and 4-dimethylaminopyridine (3 mg, 0.025 mmol). The reaction mixture was heated under nitrogen at 100° C. for 1 h, then cooled to room temperature. The mixture was diluted with ethyl acetate, washed with 1N HCl aqueous solution and H2O. The organic layer was separated, dried over Na2SO4 and concentrated. The residue was purified by chromatography (MeOH:EtOAc=1:19) to give racemic(2′R, 3R, 4′S)-2′-{5-Bromo-2-[4-(2-hydroxy-1,1-dimethyl-ethylcarbamoyl)-phenoxy]-phenyl}-6-chloro-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield: 84 mg, 42%).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with 1N HCl aqueous solution and H2O
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (MeOH:EtOAc=1:19)

Sources & evidence

ORD record
ord-2b8f86e2a7df44f7b36939b5b9150869
Source dataset
uspto-grants-2012_03
Patent number
US08134001B2

Reaction notes

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