Pyridine → HCID 89955707, compound

HRID 1481271Notes

Reaction equation

HRID 1481271 reaction equation
[CH3:1][O:2][C:3](=[O:30])[NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([C@@H:17]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH:19]=[CH2:20])[CH:12]=2)=[C:7]([NH2:29])[CH:6]=1.N1C=CC=C[CH:32]=1.C(P1(=O)OP(CCC)(=O)OP([CH2:51][CH2:52][CH3:53])(=O)O1)CC.C[CH2:56][O:57]C(C)=O>>[C:25]([O:24][C:22]([NH:21][C@H:17]([C:13]1[CH:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([NH:4][C:3](=[O:30])[O:2][CH3:1])=[CH:6][C:7]=2[NH:29][C:56](=[O:57])[C@H:52]([CH3:53])[CH:51]=[CH2:32])[CH:16]=[CH:15][N:14]=1)[CH2:18][CH:19]=[CH2:20])=[O:23])([CH3:26])([CH3:28])[CH3:27]

Participants

5

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 66744781HCID 66744781, compound

Product 1

HCID 89955707HCID 89955707, compoundYield 97%

Conditions

Temperature
-10 °C

Procedure

Intermediate 10 (1.201 g, 12.00 mmol), 1F (3.3 g, 8.00 mmol), pyridine (1.937 ml, 24.00 mmol) in EtOAc (40.0 ml) was cooled down to −10° C. under Ar, T3P (50% wt in EtOAc) (9.52 ml, 16.00 mmol) was added dropwise and stirred at −10° C., then gradually warmed up to rt over night. The reaction mixture was washed with sat. aq. NaHCO3 twice, combined aqueous layer was back extracted with EtOAc. The combined EtOAc phases washed with brine, dried over MgSO4, filtered, concentrated. The crude product was then purified using silica gel chromatography to give 1G (4.06 g, 97%) as a white solid. 1H NMR (500 MHz, METHANOL-d4) δ 8.46 (d, J=5.0 Hz, 1H), 7.64 (s, 1H), 7.47 (dd, J=8.4, 2.1 Hz, 1H), 7.35 (s, 1H), 7.29 (d, J=8.3 Hz, 1H), 7.25 (m, 1H), 5.87-5.73 (m, 2H), 5.16-5.02 (m, 4H), 4.79-4.71 (m, 1H), 3.75 (s, 3H), 3.14-3.05 (m, 1H), 2.64-2.55 (m, 1H), 2.52-2.43 (m, 1H), 1.42 (s, 9H), 1.16 (d, J=6.9 Hz, 3H). MS (ESI) m/z: 495.1 (M+H)+.

Workup

  1. additionwas added dropwise
  2. temperaturegradually warmed up to rt over night
  3. washThe reaction mixture was washed with sat. aq. NaHCO3 twice
  4. extractionwas back extracted with EtOAc
  5. washThe combined EtOAc phases washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was then purified

Sources & evidence

ORD record
ord-1f6f5214ea9944e58a8d3c13233d6711
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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