Boron tribromide → HCID 178429074, compound

HRID 2174101Notes

Reaction equation

HRID 2174101 reaction equation
[NH2:1][C:2]([C:19]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:21]=2[N:20]=1)([C:7]1[C:15]([O:16]C)=[CH:14][C:13]([CH3:18])=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2)[C:3]([F:6])([F:5])[F:4].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CCOC(C)=O>[NH2:1][C:2]([C:19]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:21]=2[N:20]=1)([C:7]1[C:15]([OH:16])=[CH:14][C:13]([CH3:18])=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2)[C:3]([F:6])([F:5])[F:4]

Participants

6

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 178489069HCID 178489069, compound

Product 1

HCID 178429074HCID 178429074, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (−)-2-(1-amino-2,2,2-trifluoro-1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile (Example 36-E-b) (63 mg, 0.158 mmol) in methylene chloride (Volume: 1.6 mL) at 0° C. was added 1 M BBr3 in DCM (315 μl, 0.315 mmol). The reaction was stirred in ice bath for 5 minutes and then the suspension was allowed to stir at room temperature for 2 hours. The reaction was poured into ice water, treated with saturated a solution of sodium bicarbonate, and then diluted with EtOAc and the EtOAc layer was removed, dried, concentrated and absorbed onto silica to purify via FCC (0-5% MeOH containing 10% ammonium hydroxide:dcm) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.55-12.76 (m, 1H) 11.01-11.28 (m, 1H) 10.82 (br. s., 1H) 8.35 (s, 1H) 7.83-8.06 (m, 1H) 7.46-7.65 (m, 2H) 6.88 (t, J=2.91 Hz, 1H) 6.50 (s, 1H) 4.84 (br. s., 1H) 2.27-2.43 (m, 3H). MS (ESI+) m/z 386.3 (M+H).

Workup

  1. customat 0° C.
  2. stirringto stir at room temperature for 2 hours
  3. customthe EtOAc layer was removed
  4. customdried
  5. concentrationconcentrated
  6. customabsorbed onto silica
  7. customto purify via FCC (0-5% MeOH containing 10% ammonium hydroxide:dcm)

Sources & evidence

ORD record
ord-08292a45efc544349f6850008a58dafd
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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