Lithium Chloride → HCID 59618815, compound

HRID 1691461Notes

Reaction equation

HRID 1691461 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:33]=1.[Li+].[Cl-].C([Sn](CCCC)(CCCC)[C:41]([O:43]CC)=[CH2:42])CCC.Cl.CCOCC>CN1C(=O)CCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:29]([C:26]1[CH:27]=[CH:28][C:23]([S:20]([N:7]2[C:6]3[CH:33]=[C:2]([C:41](=[O:43])[CH3:42])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:18])([F:17])[F:19])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:21])=[O:22])=[CH:24][CH:25]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 433294Lithium ChlorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 10953452Ether hydrochlorideHCID 596186368-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×

Product 1

HCID 59618815HCID 59618815, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (270 mg, 0.5 mmol, from intermediate 53, Pd(dppf)Cl2 (165 mg, 0.2 mmol), and LiCl (21 mg, 0.5 mmol) were dissolved in NMP (1.5 mL) under N2 was added tri-n-butyl(1-ethoxyvinyl)tin (180 mg, 0.5 mmol), and the resulting mixture was stirred at 90° C. for 1 h. The cooled reaction mixture was poured into 1M HCl/Et2O (5 mL) and stirred vigorously for 2 h. The product was extracted with EtOAc and the combined extracts were washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by SiO2 column chromatography to provide the title compound. LC/MS: m/e 504.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 8.19 (1H, s), 7.92 (1H, d, J=8.4 Hz), 7.64 (1H, d, J=7.6 Hz), 7.15 (1H, d, J=7.5 Hz), 7.12 (2H, d, J=8.4 Hz), 7.01 (1H, s), 6.94 (2H, d, J=8.2 Hz), 6.83 (1H, d, J=8.4 Hz), 4.65-4.9 (2H, br), 2.64 (3H, s), 1.25 (9H, s).

Workup

  1. customThe cooled reaction mixture
  2. stirringstirred vigorously for 2 h
  3. extractionThe product was extracted with EtOAc
  4. washthe combined extracts were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by SiO2 column chromatography

Sources & evidence

ORD record
ord-af8771fa357e41048da5908300becbd4
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

Loading…