Boron tribromide → HCID 86297634, compound

HRID 1505663Notes

Reaction equation

HRID 1505663 reaction equation
C[O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]#[N:13])[NH:9]2)=[CH:5][C:4]=1[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[C:23]3[CH:30]=[C:29]([CH2:31][C:32]([F:35])([F:34])[F:33])[S:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:17][CH2:16]1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[OH:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]#[N:13])[NH:9]2)=[CH:5][C:4]=1[CH2:14][N:15]1[CH2:16][CH2:17][CH:18]([NH:21][C:22]2[C:23]3[CH:30]=[C:29]([CH2:31][C:32]([F:34])([F:35])[F:33])[S:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 90405035HCID 90405035, compound

Product 1

HCID 86297634HCID 86297634, compoundYield 61.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

500 mg of 6-methoxy-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile (1 mmol) was slowly added to 5 mL of 1M BBr3 in DCM at 0 degrees and reaction mixture was brought to RT. After 4days ice was added to reaction mixture in the presence of sodium bicarbonate. Volatile organic was evaporated and the residue was partitioned between water and ethyl acetate-methanol 10:1. Organic layer was evaporated with silica gel and loaded on the column. The product was eluted with hexane-ethyl acetate-methanol 1:1:0.1, evaporation of fractions produced 300 mg of 6-hydroxy-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile (Compound 182). Its monohydrochloride salt was obtained by adding 1 equivalent of 1N HCl solution in diethyl ether to a solution of compound in ethanol. Monohydrochloride salt exists as a mixture of rotomers in approximate ratio 10:1, NMR is described for the major one: 1H NMR (600 MHz, MeOD-d4): 8.70 (s, 1H), 7.81 (s, 1H), 7.77 (s, 1H), 7.21 (s, 1H), 6.98 (s, 1H), 4.64 (m, 1H), 4.48 (s, 1H), 4.01 (q, 2H, J=10.3 Hz), 3.66 (m, 2H), 3.35 (m, 2H), 2.37 (m, 2H), 2.12 (m, 2H). 13C NMR (150 MHz, MeOD-d4): δC 157.64, 156.62, 153.92, 141.09, 130.54, 127.75, 127.48, 125.65, 121.96, 121.59, 118.27, 115.23, 114.85, 113.98, 107.11, 97.45, 57.78, 52.88, 47.29, 35.54 (q, J=33 Hz), 29.95. ESI MS [MH+]: 487.1519.

Workup

  1. customreaction mixture
  2. customwas brought to RT
  3. customVolatile organic was evaporated
  4. customthe residue was partitioned between water and ethyl acetate-methanol 10:1
  5. customOrganic layer was evaporated with silica gel
  6. washThe product was eluted with hexane-ethyl acetate-methanol 1:1:0.1, evaporation of fractions

Sources & evidence

ORD record
ord-1877d8a05f134de4b460beb6d8708bba
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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