Benzylamine → trans-2,2,2-trifluoro-N-[2,3,4,14b-tetrahydro-7-[(phenylmethyl)amino]-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl]acetamide

HRID 16178Notes

Reaction equation

HRID 16178 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]2[O:6][C:7]3[CH:25]=[CH:24][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(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[CH2:55]([NH2:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:17]([F:20])([F:19])[C:16]([NH:15][C@H:14]1[C@@H:9]2[N:10]([C:4]3[CH:3]=[C:2]([NH:62][CH2:55][C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[CH:27]=[CH:26][C:5]=3[O:6][C:7]3[CH:25]=[CH:24][CH:23]=[CH:22][C:8]=32)[CH2:11][CH2:12][CH2:13]1)=[O:21]

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86599888trans-N-(7-bromo-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]-oxazepin-1-yl)-2,2,2-trifluoroacetamide

Product 1

HCID 86599889trans-2,2,2-trifluoro-N-[2,3,4,14b-tetrahydro-7-[(phenylmethyl)amino]-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl]acetamideYield 32%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of trans-N-(7-bromo-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]-oxazepin-1-yl)-2,2,2-trifluoroacetamide (0.5 g, 1.1 mmol) in DME (16 mL), Pd2(dba)3 (12.5 mg, 13.5 μmol), 2-(di-t-butyl-phosphino)biphenyl (25 mg, 80 μmol), sodium-tert-butoxide (218 mg, 2.3 mmol) and benzylamine (243 mg, 2.3 mmol) were added. The resulting reaction mixture was heated to 75° C. and stirred at this temperature for 48 h. The reaction mixture was quenched with sat NaHCO3 (aq) and extracted with ethyl acetate. The organic layer was washed with water and brine, dried (Na2SO4) and evaporated. The crude product was chromatographed with heptane/ethyl acetate 8:2 and purified with HPLC to afford the title compound (21 mg, 32%). Data: 1H-NMR (400 MHz, DMSO) 1.54-2.02 (m, 4H), 2.95 (t, J=9.2, 1H), 3.68 (d, J=14.0, 1H), 4.02 (d, J=10.0, 1H), 4.17 (d, J=6.0, 2H), 4.37 (m, 1H), 5.90-7.33 (12 ArH, 1 NH), 9.11 (d, J=10.0, 1H). (m/z)=468 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customThe reaction mixture was quenched with sat NaHCO3 (aq)
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe crude product was chromatographed with heptane/ethyl acetate 8:2
  8. custompurified with HPLC

Sources & evidence

ORD record
ord-acabd88f6b8b48108a0dbcbca4318b9f
Source dataset
uspto-grants-2010_06
Patent number
US07737136B2

Reaction notes

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