Phosphorus oxychloride → HCID 178454097, compound

HRID 532527Notes

Reaction equation

[C:1]([C:4]1[NH:8][N:7]=[C:6]2[CH2:9][N:10]([C@H:12]3[CH2:17][S:16][CH:15]([C:18]4[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=4[F:25])[C@@H:14]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:13]3)[CH2:11][C:5]=12)(=O)[NH2:2].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([C:4]1[NH:8][N:7]=[C:6]2[CH2:9][N:10]([C@H:12]3[CH2:17][S:16][CH:15]([C:18]4[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=4[F:25])[C@@H:14]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:13]3)[CH2:11][C:5]=12)#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of tert-butyl N-[(3S,5R)-5-(3-carbamoyl-4,6-dihydro-2H-pyrrolo[3,4-c]pyrazol-5-yl)-2-(2,5-difluorophenyl)tetrahydrothiopyran-3-yl]carbamate (35 mg, 0.073 mmol) in pyridine (4 mL) was added phosphorous oxychloride (0.020 mL, 0.219 mmol) at 0° C. under nitrogen. The resulting mixture was stirred at 0° C. for 5.5 h, quenched with water (0.2 mL) and the solvents were removed under vacuum. The residue was diluted with ethyl acetate (200 mL), washed with saturated aqueous sodium hydrogen carbonate (1×150 mL), brine, dried with sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by prep-TLC, eluting with 8% MeOH (1N NH3 in MeOH) in CH2Cl2, to give the title compound. MS: 462.1

Workup

customquenched with water (0.2 mL)
customthe solvents were removed under vacuum
additionThe residue was diluted with ethyl acetate (200 mL)
washwashed with saturated aqueous sodium hydrogen carbonate (1×150 mL), brine
dry with materialdried with sodium sulfate
filtrationfiltered
customevaporated under reduced pressure
customThe residue was purified by prep-TLC,
washeluting with 8% MeOH (1N NH3 in MeOH) in CH2Cl2

Sources & evidence

ORD record: ord-b01b3f9b887c480e950958346823a24f
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853212B2

Reaction notes

Loading…