Phosphorus oxychloride → HCID 86678988, compound

HRID 2203354Notes

Reaction equation

HRID 2203354 reaction equation
[NH2:1][C:2]1[C:3]2[C:28]([CH:32]3[CH2:34][CH2:33]3)([C:29]([NH2:31])=O)[C:27](=[O:35])[NH:26][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])[N:9]=2)[N:7]=1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[NH2:1][C:2]1[C:3]2[C:28]([CH:32]3[CH2:34][CH2:33]3)([C:29]#[N:31])[C:27](=[O:35])[NH:26][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:21])([F:23])[F:22])[N:9]=2)[N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86678989HCID 86678989, compound

Product 1

HCID 86678988HCID 86678988, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

4-amino-5-cyclopropyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, as described in Example 162, (565 mg, 1.201 mmol) was taken up in pyridine (6 mL) and the solution cooled to 0° C. Phosphorous oxychloride (0.896 ml, 9.61 mmol) was then added dropwise and the reaction mixture was warmed to room temperature. After 15 minutes, the pyridine solvent was concentrated in vacuo and the residue taken up in EtOAc. The mixture was then washed with water, brine and dried over sodium sulfate. The residue was purified by silica gel column chromatography using a hexanes/EtOAc gradient to give the title compound, Chiral separation by SFC provided both enantiomers of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 9.07 (1H, d, J=8.07 Hz), 8.69 (1H, d, J=4.42 Hz), 7.44 (1H, dd, J=8.08, 4.48 Hz), 7.16 (2H, s), 4.93 (2H, t, J=6.82 Hz), 3.08-2.95 (2H, m), 1.80-1.73 (1H, m), 0.93-0.88 (1H, m), 0.65 (2H, d, J=8.31 Hz), 0.55-0.48 (1H, m). m/z=479.1 (M+H).

Workup

  1. temperaturethe reaction mixture was warmed to room temperature
  2. concentrationthe pyridine solvent was concentrated in vacuo
  3. washThe mixture was then washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. customThe residue was purified by silica gel column chromatography
  6. customto give
  7. customthe title compound, Chiral separation by SFC

Sources & evidence

ORD record
ord-68a8fcefb972410d8d690c553ef68163
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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