Bromotrimethylsilane → HCID 178482412, compound

HRID 472106Notes

Reaction equation

HRID 472106 reaction equation
[CH3:1][N:2]([C:20]1[C:21]2[CH:28]=[CH:27][NH:26][C:22]=2[N:23]=[CH:24][N:25]=1)[C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][S:10]([N:13]2[CH2:18][CH2:17][CH2:16][C@@H:15]([OH:19])[CH2:14]2)(=[O:12])=[O:11])[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[P:38](OCl)([O:43]CC)([O:40]CC)=[O:39].Br[Si](C)(C)C>ClCCl.CO>[P:38]([OH:43])([OH:40])([O:19][C@@H:15]1[CH2:16][CH2:17][CH2:18][N:13]([S:10]([CH2:9][C@H:6]2[CH2:5][CH2:4][C@H:3]([N:2]([CH3:1])[C:20]3[C:21]4[CH:28]=[CH:27][NH:26][C:22]=4[N:23]=[CH:24][N:25]=3)[CH2:8][CH2:7]2)(=[O:12])=[O:11])[CH2:14]1)=[O:39]

Participants

7

Reactant 4

HCID 76113BromotrimethylsilaneHCID 81531DiisopropylethylamineHCID 22262455HCID 22262455, compoundHCID 178482410HCID 178482410, compound

Product 1

HCID 178482412HCID 178482412, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(3R)-1-[({trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-methyl)sulfonyl]piperidin-3-ol (100 mg, 0.24 mmol) was suspended in dichloromethane (5 mL). Diisopropylethylamine (0.05 mL, 0.3 mmol) was added followed by diethyl chloro phosphate (0.036 mL, 0.24 mmol). The reaction mixture was stirred under nitrogen overnight. Methanol (1 mL) was added to the flask and the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (10 mL) and bromotrimethylsilane (2 mL, 14.4 mmol) was added. The reaction mixture was stirred under nitrogen at room temperature for 18 hours and then was concentrated in vacuo. The residue was purified by reverse phase HPLC. (2 mg, 5%). 1H NMR (400 MHz, DMSO-d6) ppm 1.28 (br. s., 1H) 1.50 (br. s., 1H) 1.63-1.72 (m, 2H) 1.86 (d, J=2.56 Hz, 1H) 2.02 (d, J=10.98 Hz, 1H) 2.83 (s, 1H) 2.94 (td, J=14.46, 6.59 Hz, 2H) 3.14 (s, 2H) 3.47 (br. s., 9H) 3.52 (br. s., 11H) 6.51 (br. s., 1H) 7.09 (d, J=2.93 Hz, 1H). LCMS m/z 488.8 (M+H calcd for C19H30N6O6PS requires 487.5). LCMS (C-18 column, gradient elution 5 minute chromatograph, 95:5 to 5:95 water/acetonitrile, retention time 1.23 min).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  3. stirringThe reaction mixture was stirred under nitrogen at room temperature for 18 hours
  4. concentrationwas concentrated in vacuo
  5. customThe residue was purified by reverse phase HPLC
  6. washLCMS (C-18 column, gradient elution 5 minute chromatograph, 95:5 to 5:95 water/acetonitrile, retention time 1.23 min)

Sources & evidence

ORD record
ord-ff825593e7a643599de125c537334120
Source dataset
uspto-grants-2014_01
Patent number
US08633206B2

Reaction notes

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