Boron tribromide → HCID 86681125, compound

HRID 1848155Notes

Reaction equation

HRID 1848155 reaction equation
C[O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide3×HCID 86681126HCID 86681126, compound

Product 1

HCID 86681125HCID 86681125, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

To a stirred solution of (1R,2R)-2-((6-((7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (45 mg, 0.099 mmol) from Example 153 in 2 mL of DCM at −10° C. was added BBr3 in DCM (1.0 M, 110 μL, 0.11 mmol). The resulting mixture was stirred at rt for 30 min before it was cooled to −10° C. and additional BBr3 in DCM (1.0 M, 100 μL, 0.10 mmol) was added. After stirring at rt overnight, BBr3 in DCM (1.0 M, 100 μL, 0.10 mmol) was added and stirring was continued for 1 d. The resulting mixture was quenched with MeOH and the mixture was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1R,2R)-2-((6-((7-(2-hydroxyethoxy)imidazo[1,2-a]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (16 mg, 37%). 1H NMR (500 MHz, DMSO-d6) δ 8.00 (d, J=7.9 Hz, 1H), 7.91 (d, J=7.4 Hz, 1H), 7.49 (s, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.22 (s, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.0 Hz, 1H), 6.57 (dd, J=2.5, 7.4 Hz, 1H), 4.79 (br s, 1H), 4.22 (s, 2H), 4.02 (t, J=4.7 Hz, 2H), 3.72 (t, J=4.7 Hz, 2H), 3.50 (br s, 2H), 2.04 (d, J=12.8 Hz, 1H), 1.87 (d, J=11.3 Hz, 1H), 1.54-1.68 (m, 2H), 1.10-1.37 (m, 4H). LCMS (ESI) m/z 439 (M+H)+.

Workup

  1. temperaturewas cooled to −10° C.
  2. stirringAfter stirring at rt overnight
  3. stirringstirring
  4. waitwas continued for 1 d
  5. customThe resulting mixture was quenched with MeOH
  6. customthe mixture was purified by reverse-phase preparative HPLC
  7. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-f80f0ae3a77c4adc8c4a845c6035224f
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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