HCID 16063296, compound → HCID 16063420, compound

HRID 2035422Notes

Reaction equation

HRID 2035422 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]([NH:5][C@@H:6]1[CH2:31][CH2:30][N:9]2[C:10]3[CH:23]=[CH:22][C:21]([C:24]4[N:25]=NN(C)N=4)=[CH:20][C:11]=3[C@H:12]([CH3:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C@H:8]2[CH2:7]1)=[O:4]>C1COCC1.N.[Zn]>[F:32][C:2]([F:1])([F:33])[C:3]([NH:5][C@@H:6]1[CH2:31][CH2:30][N:9]2[C:10]3[CH:23]=[CH:22][C:21]([C:24]4[CH:2]=[CH:3][N:5]=[CH:6][N:25]=4)=[CH:20][C:11]=3[C@H:12]([CH3:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C@H:8]2[CH2:7]1)=[O:4]

Participants

5

Reactant 1

HCID 16063296HCID 16063296, compound

Product 1

HCID 16063420HCID 16063420, compoundYield 170.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 222AmmoniaSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 10 (R8═C4H2N2Cl, R2═COCF3; 614 mg, 1.26 mmol) in THF (50 mL) and ammonia (22 mL), zinc (2.17 g 33.2 mmol) was added. The reaction mixture was stirred for 5 hours under reflux. The reaction was quenched with a saturated NaHCO3 solution in H2O and filtered over decalite. The product was extracted into ethyl acetate, washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica affording rel-2,2,2-trifluoro-N-[(2R,10R,14bR)-1,2,3,4,10,14b-hexahydro-10-methyl-8-(pyrimidin-4-yl)dibenzo[c,f]pyrido[1,2-a]azepin-2-yl]acetamide (10: R8═C4H3N2, R2═COCF3; 485 mg, 85%). Data: (m/z)=453 (M+H)+.

Workup

  1. temperatureunder reflux
  2. customThe reaction was quenched with a saturated NaHCO3 solution in H2O
  3. filtrationfiltered over decalite
  4. extractionThe product was extracted into ethyl acetate
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica

Sources & evidence

ORD record
ord-f9946e3cf3cc482a92da41bcedb2aff9
Source dataset
uspto-grants-2013_11
Patent number
US08575152B2

Reaction notes

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