Cyanomethylenetrimethylphosphorane → HCID 178455326, compound

HRID 920659Notes

Reaction equation

HRID 920659 reaction equation
[Br:1][C:2]1[C:10]2[CH:9]=[N:8][C:7]([Cl:11])=[N:6][C:5]=2[NH:4][CH:3]=1.[Si:12]([O:19][C@@H:20]1[CH2:25][CH2:24][C@H:23](O)[CH2:22][CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].C(C=P(C)(C)C)#N>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:10]2[CH:9]=[N:8][C:7]([Cl:11])=[N:6][C:5]=2[N:4]([C@H:23]2[CH2:24][CH2:25][C@H:20]([O:19][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:14])[CH2:21][CH2:22]2)[CH:3]=1

Participants

5

Reactant 3

HCID 11094579CyanomethylenetrimethylphosphoraneHCID 457897805-Bromo-2-chloro-7H-pyrrolo[2,3-d]pyrimidineHCID 178455370HCID 178455370, compound

Product 1

HCID 178455326HCID 178455326, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 5-bromo-2-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.13 g, 0.50 mmol) and cis-4-(tert-butyldimethylsilyloxy)cyclohexanol (0.23 g, 1.0 mmol) in toluene (8 mL) was added (cyanomethylene)trimethylphosphorane (CMMP; prepared according to Chem. Pharm. Bull. 2003, 51(4), 474-476.) (6.3 mL, 0.16 M in THF, 1.0 mmol). The resulting clear solution was refluxed for 16 h. The reaction mixture was washed with brine, and extracted with EtOAc (3×). The combined organic layer was dried (Na2SO4) and concentrated. The residue was purified on ISCO to provide the desired product (0.16 g, 72%). 1H NMR (400 MHz, CD3OD) δ 8.71 (s, 1H), 7.27 (s, 1H), 4.70 (tt, J=12.2, 3.9 Hz, 1H), 3.69 (tt, J=10.5, 4.2 Hz, 1H), 2.09-1.99 (m, 3H), 1.86-1.71 (m, 2H), 1.66-1.54 (m, 3H), 0.90 (s, 9H), 0.08 (s, 6H). MS m/z 444.2 [M+H]+.

Workup

  1. temperatureThe resulting clear solution was refluxed for 16 h
  2. washThe reaction mixture was washed with brine
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified on ISCO

Sources & evidence

ORD record
ord-5e4ed1bd6d97427d8b2a2da250f8c759
Source dataset
uspto-grants-2016_03
Patent number
US09273056B2

Reaction notes

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