(Diethylamino)sulfur trifluoride → HCID 131731145, compound

HRID 471890Notes

Reaction equation

HRID 471890 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH2:12][C:11]3([CH2:18][C@@H:17](O)[CH2:16][C@H:15]([NH:20][C:21]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[N:24]=4)=[O:22])[CH2:14]3)[C:10]2=[O:30])[CH:5]=[C:6]([F:8])[CH:7]=1.CCN(S(F)(F)[F:37])CC>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C:11]3([CH2:18][C@@H:17]([F:37])[CH2:16][C@H:15]([NH:20][C:21]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[N:24]=4)=[O:22])[CH2:14]3)[C:10]2=[O:30])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 131731146HCID 131731146, compound

Product 1

HCID 131731145HCID 131731145, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluorophenyl)-9-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide (crude, <0.121 mmol) in DCM (5 mL) was added DAST (20.3 μL, 0.154 mmol) at 0° C. The reaction mixture was stirred at room temperature overnight and quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel (0 to 70% EtOAc in hexanes) to give 2 mg of the title compound, trans-2-methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9-fluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide. 1H NMR (400 MHz, CDCl3) δ 8.79 (d, J=5.0 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.82 (t, J=5.0 Hz, 1H), 7.26-7.21 (m, 1H), 6.54 (tt, J=8.8, 2.2 Hz, 1H), 5.22-5.05 (m, 1H), 4.55-4.43 (m, 1H), 3.79-3.66 (m, 2H), 2.71 (s, 3H), 2.45-2.25 (m, 3H), 2.09-1.92 (m, 3H), 1.74-1.54 (m, 2H). ESI-MS m/z: 419 (M+H)+.

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. extractionThe aqueous layer was extracted with DCM
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel (0 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-214b052f10554e248db714d5ce7e1d27
Source dataset
uspto-grants-2014_01
Patent number
US08633190B2

Reaction notes

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