Methanol → HCID 57463191, compound

HRID 1783837Notes

Reaction equation

HRID 1783837 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]([C:38]#[N:39])[CH:33]=4)[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Br-].[Br-].[Br-].B.C[OH:45]>ClCCl>[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]([CH:35]=[CH:36][CH:37]=4)[C:38]([NH2:39])=[O:45])[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 57463153HCID 57463153, compoundHCID 178419136HCID 178419136, compound

Product 1

HCID 57463191HCID 57463191, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-cyano-phenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.50 g, 0.87 mmol) in dichloromethane (DCM) (10 mL) at −78° C. was added a solution of borane tribromide (BBr3) (1.74 mL, 1.0 M in DCM). The mixture was stirred at −78° C. for 0.5 hour, then room temperature for one hour. The mixture was then cooled to −78° C. and methanol (1 mL) was added. The resulting mixture was stirred at room temperature overnight. Solvent was removed in vaco, the residue was treated with a 1:1 mixture of dichloromethane and water (50 mL). Organic layer was separated, dried over sodium sulfate and concentrated. Product was purified by flash chromatography on silica gel eluting with 5% methanol in dichloromethane to afford 0.019 g (4%) of the title compound as a yellow solid. M.p.=168-170° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.70 (br. s, 1H), 8.10 (s, 1H), 8.10 (d, J=4.8 Hz, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.94-7.80 (m, 1 H), 7.77-7.65 (m, 4H), 7.53 (t, J=8.0 Hz, 1H), 7.42 (d, J=4.4 Hz, 1H), 7.25-7.13 (m, 2H), 7.15 (d, J=7.2 Hz, 1H), 6.34 (d, J=5.6 Hz, 1H), 3.92 (bs, 1H), 3.73 (d, J=8.4 Hz, 1H), 3.48 (d, J=11.2 Hz, 1H), 2.48-2.43 (m, 1H), 2.35 (t, J=10.8 Hz, 1H), 1.90-1.82 (m, 2H), 1.59-1.56 (m, 1H), 1.39-1.34 (m, 1H). LCMS: 595 [M+H].

Workup

  1. waitroom temperature for one hour
  2. temperatureThe mixture was then cooled to −78° C.
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. customSolvent was removed in vaco
  5. additionthe residue was treated with a 1:1 mixture of dichloromethane and water (50 mL)
  6. customOrganic layer was separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customProduct was purified by flash chromatography on silica gel eluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-ae10437384e8439c99f41ed7d0798448
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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