Boron tribromide → HCID 178422184, compound

HRID 2361306Notes

Reaction equation

HRID 2361306 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:36])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([O:31]C)=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:33]([NH2:35])=[O:34])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1.BrB(Br)Br.C([O-])(O)=O.[Na+]>ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:36])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([OH:31])=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:33]([NH2:35])=[O:34])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 67994719HCID 67994719, compound

Product 1

HCID 178422184HCID 178422184, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a heterogeneous mixture of 4-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-methoxy-9H-pyrido[3,4-b]indole-1-carboxamide (prepared in the same manner as Example 15) (0.277 g, 0.557 mmol) in dichloromethane (20 mL) at 0° C. was added tribromoborane in dichloromethane (2.79 mL, 2.79 mmol) over 5 min. The heterogeneous mixture was stirred at room temperature for 3 hr and then poured into ice cold water (20 mL). The resulting mixture was basified with saturated NaHCO3 solution to pH 8 and extracted with ethyl acetate (3×40 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (0.217 g, 85% purity, 0.382 mmol, 68.5% yield) as a yellow solid. A pure sample was obtained through prep. reverse phase HPLC purification. LCMS (M+H)+=483.15. 1H NMR (500 MHz, DMSO-d6) δ: 11.61 (s, 1H), 9.89 (s, 1H), 8.34 (s, 1H), 8.20 (s, 1H), 7.88 (s, 1H), 7.81-7.77 (m, 3H), 7.72 (dd, J1=7.8 Hz, J2=1.2 Hz, 1H), 7.58 (m, 1H), 7.48 (dd, J1=7.5 Hz, J2=1.2 Hz, 1H), 7.23 (d, J=2.0 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 6.60 (dd, J1=8.7 Hz, J2=2.3 Hz, 1H), 5.10 (d, J=17.6 Hz, 1H), 4.99 (d, J=17.6 Hz, 1H), 1.92 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×40 mL)
  2. extractionThe combined extract
  3. washwas washed with brine (30 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-e9a90c17b7b44aaa9d28ca903cd931e5
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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