Boron tribromide → HCID 24758002, compound

HRID 1783805Notes

Reaction equation

HRID 1783805 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[N:31]5[C:27]([S:28][CH:29]=[CH:30]5)=[N:26][C:25]=4[C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([O:38]C)[CH:33]=4)[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[N:31]5[C:27]([S:28][CH:29]=[CH:30]5)=[N:26][C:25]=4[C:32]4[CH:33]=[C:34]([OH:38])[CH:35]=[CH:36][CH:37]=4)[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 57463131HCID 57463131, compound

Product 1

HCID 24758002HCID 24758002, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-methoxy-phenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (6.98 g, 12.03 mmol) in methylene chloride (100 ml) was cooled to −78° C. and slowly treated with 1 molar solution of boron tribromide in methylene chloride (65 ml). The reaction mixture was kept at −78° C. for one hour then was allowed to warm to room temperature for two hours. The mixture was quenched by the addition of methanol (25 ml) at 0° C. and was stirred at room temperature for an additional hour. The mixture was diluted with methylene chloride (500 ml) and washed with three portions of 100 ml of saturated sodium bicarbonate solution, two portions of 100 ml of water and two portions of 100 ml of saturated sodium chloride solution. The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow foam. The crude product was re-crystallized from methanol as a yellow solid (4.85 g, 71%). M.p.=174-177° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 9.4 (br. s, 1H), 8.70 (br. s, 1H), 8.12 (d, J=5.5 Hz, 1H), 7.8-7.7 (m, 2H), 7.7-7.65 (m, 2H), 7.40 (d, J=4.7 Hz, 1H), 7.25 (t, J=8.0 Hz, 1H), 7.15 (d, J=7.4 Hz, 1H), 7.0-6.95 (m, 1H), 6.85-6.8 (m, 1H), 6.44 (d, J=5.5 Hz, 1H), 3.95 (br. s, 1H), 3.72 (dd, J=10.6 3.1 Hz, 1H), 3.40 (m, 1H), 2.5-2.4 (m, 1H), 2.35 (t, J=10.2 Hz, 1H), 2.0-1.8 (m, 2H), 1.65-1.5 (m, 1H), 1.46-1.32 (m, 1H). LCMS: 567 [M+H]. Calc. for C26H23N6O3S2Cl.0.5 water.1.0 methanol: C, 53.33; H, 4.64; N, 13.82. Found C, 53.32; H, 4.64; N, 13.82.

Workup

  1. customThe mixture was quenched by the addition of methanol (25 ml) at 0° C.
  2. additionThe mixture was diluted with methylene chloride (500 ml)
  3. washwashed with three portions of 100 ml of saturated sodium bicarbonate solution, two portions of 100 ml of water and two portions of 100 ml of saturated sodium chloride solution
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customgiving a yellow foam
  7. customThe crude product was re-crystallized from methanol as a yellow solid (4.85 g, 71%)

Sources & evidence

ORD record
ord-44a367ad8742466c80c2d374be86b968
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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