Boron tribromide → HCID 17747249, compound

HRID 1783830Notes

Reaction equation

HRID 1783830 reaction equation
[CH:1]1([S:4]([N:7]2[CH2:12][CH2:11][CH:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[N:27]5[C:23]([S:24][CH:25]=[CH:26]5)=[N:22][C:21]=4[C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([O:35]C)[CH:29]=4)[CH:17]=[CH:16][N:15]=3)[CH2:9][CH2:8]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.B(Br)(Br)Br>C(Cl)Cl>[CH:1]1([S:4]([N:7]2[CH2:8][CH2:9][CH:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[N:27]5[C:23]([S:24][CH:25]=[CH:26]5)=[N:22][C:21]=4[C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([OH:35])[CH:29]=4)[CH:17]=[CH:16][N:15]=3)[CH2:11][CH2:12]2)(=[O:5])=[O:6])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 57433764HCID 57433764, compound

Product 1

HCID 17747249HCID 17747249, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The N-[1-(cyclopropylsulfonyl)piperidin-4-yl]-4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.226 g, 0.43 mmol) in methylene chloride (8 ml) was cooled to −78° C. and slowly treated with 1 molar solution of boron tribromide in methylene chloride (3.4 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 (900 μl) at −78° C. and was stirred at room temperature for an additional hour. The mixture was diluted with methylene chloride (100 ml) and washed with three portions of 25 ml of saturated sodium bicarbonate solution, two portions of 25 ml of water and two portions of 25 ml of saturated sodium chloride solution. The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow solid. The crude product was purified by flash chromatography (ethyl acetate), affording 0.19 g (86%) of the title compound as a beige solid. M.p.=224-225° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 9.82 (s, 1H), 8.67 (br. s, 1H), 8.12 (d, J=5.5 Hz, 1H), 7.43 (d, J=4.3 Hz, 1H), 7.25-7.14 (m, 3H), 6.99 (ddd, J=8.2, 4.3, 2.0 Hz, 1H), 6.41 (d, J=5.1 Hz, 1H), 3.95-3.84 (m, 1H), 3.68-3.60 (m, 2H), 3.00 (td, J=11.9, 2.7 Hz, 2H), 2.59-2.52 (m, 1H), 2.06-1.98 (m, 2H), 1.66-1.54(m, 2H), 1.04-0.92 (m, 4H). LCMS: 515 [M+H]. Calc. for C23H23N6O3S2F.0.53 diethyl ether.0.17 water: C, 53.46; H, 4.93; N, 14.89. Found C, 53.46; H, 4.60; N, 14.88.

Workup

  1. customThe mixture was quenched by the addition of methanol (900 μl) at −78° C.
  2. additionThe mixture was diluted with methylene chloride (100 ml)
  3. washwashed with three portions of 25 ml of saturated sodium bicarbonate solution, two portions of 25 ml of water and two portions of 25 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 solid
  7. customThe crude product was purified by flash chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-e48581f19f644b8a9f2e315f6deca415
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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