Water → (-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide

HRID 1668360Notes

Reaction equation

HRID 1668360 reaction equation
Br[C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[C:30]([Cu])#[N:31].CN1C(=O)CCC1.O>C(OCC)(=O)C.[Cu]I>[C:30]([C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:18])[F:19])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1)#[N:31]

Participants

7

Reactant 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 86619616(-)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamideHCID 178418546HCID 178418546, compound

Product 1

HCID 86619617(-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamideYield 59.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 2.74 g (5.74 mmol) of (−)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide, CuCN (1.3 g, 14.3 mmol), CuI (0.123 g, 0.57 mmol) and NMP (25 mL) was stirred in a microwave for 20 min. at 180° C., 300 Watt with cooling. After cooling down, the reaction mixture was poured into water (500 mL). The precipitate, containing product and salts, was redissolved in ethyl acetate and the salts were filtered off. The organic layer was washed with NH4OH-solution, water, and brine, dried, and concentrated to give the crude compound which was crystallized to give the title compound (1.45 g, 59%). 1H-NMR (400 MHz, DMSO) 1.60-1.86 (m, 3H), 2.01 (m, 1H), 3.15 (m, 1H), 3.86 (m, 1H), 4.133 (d, J=10.0, 1H), 4.35 (m, 1H), 7.00 (m, 1H), 7.03 (m, 1H), 7.44 (d, J=7.7, 1H), 7.6 (d, J=6.3, 1H), 9.23 (br-d, J=7.8, 1H). (m/z)=424 (M+H)+.

Workup

  1. temperature300 Watt with cooling
  2. temperatureAfter cooling down
  3. additionThe precipitate, containing product and salts
  4. filtrationthe salts were filtered off
  5. washThe organic layer was washed with NH4OH-solution, water, and brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude compound which
  9. customwas crystallized

Sources & evidence

ORD record
ord-2ee863f7a7354cff859c805986182d36
Source dataset
uspto-grants-2011_08
Patent number
US07989442B2

Reaction notes

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