Water → HCID 71253279, compound

HRID 1775040Notes

Reaction equation

HRID 1775040 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:28][CH2:27][CH2:26][C@H:25]([NH:29]C(=O)OCC6C=CC=CC=6)[CH2:24][CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][N:13](C4CCCCO4)[C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1.B(Br)(Br)Br.C(OCC)(=O)C.O>C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:28][CH2:27][CH2:26][C@H:25]([NH2:29])[CH2:24][CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][NH:13][C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 71261626HCID 71261626, compound

Product 1

HCID 71253279HCID 71253279, compoundYield 8.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of benzyl (4S)-1-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)azepan-4-ylcarbamate (70.0 mg, 0.13 mmol) in DCM (5.0 mL) at −10° C. was added dropwise 1 M of boron tribromide in DCM (0.33 mL, 0.33 mmol), and the reaction mixture was slowly warmed to room temperature (RT) and stirred at RT under N2 for 16 h. The reaction mixture was diluted into ethyl acetate and water. The organic layer was washed with aqueous saturated sodium bicarbonate solution, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was redissolved in DMSO (1 mL) and was purified by reverse phase HPLC to give 227 as a white solid (4.3 mg, 8.3%). 1H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 8.55 (s, 1H), 8.11 (s, 1H), 7.83 (s, 1H), 7.60 (t. J=7.8 Hz, 1H), 7.37 (d, J=7.1 Hz, 1H), 6.61 (d, J=8.4 Hz, 1H), 3.91 (s, 3H), 3.85-3.75 (m, 1H), 3.74-3.58 (m, 2H), 3.33-3.40 (m, 1H), 2.95-2.85 (m, 1H), 2.12-1.93 (m, 2H), 1.86-1.58 (m, 3H), 1.56-1.33 (m, 2H); 2 protons not seen. LC/MS: m/z 389.4 [M+1]

Workup

  1. washThe organic layer was washed with aqueous saturated sodium bicarbonate solution, water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe crude was redissolved in DMSO (1 mL)
  6. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e245ba2e24f8443ea1f3d4a1a8e0ce51
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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