(2,4-Dichlorophenyl)boronic acid → (+/-)-cis-6-(2,4-Dichlorophenyl)-1,2,3,4,7b,8,9,10,11,11a-decahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indole

HRID 23269

Reaction equation

HRID 23269 reaction equation
FC1C=CC=C(F)C=1[C:9]1[CH:10]=[C:11]2[C:15]3=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:14]3[C@H:13]3[CH2:22][CH2:23][NH:24][CH2:25][C@@H:12]23)[CH:17]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1B(O)O.[OH-].[Ba+2].[OH-]>COCCOC.C(OCC)(=O)C.O>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:9]1[CH:10]=[C:11]2[C:15]3=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:14]3[C@H:13]3[CH2:22][CH2:23][NH:24][CH2:25][C@@H:12]23)[CH:17]=1

Participants

7

Reactant 3

HCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 6093286Barium hydroxideHCID 69804117(+/-)-cis-6-(2,6-Difluorophenyl)-1,2,3,4,7b,8,9,10,11,11a-decahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indole

Product 1

HCID 69799752(+/-)-cis-6-(2,4-Dichlorophenyl)-1,2,3,4,7b,8,9,10,11,11a-decahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

tert-butyl (±)Cis-bromo-4-oxo-1,2,3,4,7b, 10,11,11 a-octahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indol-9(8H)-carboxylate from EXAMPLE 70, Part E (150 mg, 0.356 mmol), 2,4-dichlorophenylboronic acid (82 mg, 0.430 mmol) and barium hydroxide (170 mg, 0.540 mmol) were dissolved in DME (7 mL) and water (4 mL), and degassed for 10 minutes under nitrogen. Tetrakis (triphenylphosphine)palladium (0) (10 mg, 0.007 mmol) was added and the reaction was heated to 90° C. for 13 h. The reaction was cooled to room temperature and diluted with ethyl acetate (20 mL) and water (20 mL). The organic layer was separated and dried over magnesium sulfate, filtered and concentrated under reduced pressure to give an oil. The oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes).). Fractions were collected, concentrated to a solid, then dissolved in 20% TFA/CHCl3 and stirred for 1 hour. The reaction solution was cooled to 0° C. in an ice bath, and basified to pH=10 with concentrated NH4OH. This was extracted with CHCl3 (3×15 ml), organics collected, dried over MgSO4 and concentrated under reduced pressure to give to give the title compound. 1H NMR (CDCl3, 300 MHz): δ 7.52 (d, 1H, J=1.8 Hz), 7.44 (d, 1H, J=1.8 Hz), 7.26-7.20 (m, 2H), 6.45 (s, 1H), 4.34 (t, 2H, J=9.2 Hz), 4.14-4.06 (m, 2H), 3.18-2.95 (m, 3H), 2.88-2.75 (m, 3H), 2.14 (s-br, 1H), 1.96-1.79 (m, 2H) ppm.

Workup

  1. customwater (4 mL), and degassed for 10 minutes under nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil
  8. customThe oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes)
  9. customFractions were collected
  10. concentrationconcentrated to a solid
  11. dissolutiondissolved in 20% TFA/CHCl3
  12. temperatureThe reaction solution was cooled to 0° C. in an ice bath
  13. extractionThis was extracted with CHCl3 (3×15 ml), organics collected
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated under reduced pressure
  16. customto give

Sources & evidence

ORD record
ord-60002948e200495aa9d924c6d2ece058
Source dataset
uspto-grants-2005_02
Patent number
US06849619B2

Linked notes

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