Phosphorus oxychloride → (S)-tert-butyl 1-((5-(5-(2-methoxybenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate

HRID 2196516Notes

Reaction equation

HRID 2196516 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:31])[C:10]([NH:12][CH2:13][C:14]1[S:18][C:17]([N:19]2[C:23]([C:24](O)=[O:25])=[CH:22][C:21]([C:27]([F:30])([F:29])[F:28])=[N:20]2)=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][O:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH2:37].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[CH3:32][O:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH:37][C:24]([C:23]1[N:19]([C:17]2[S:18][C:14]([CH2:13][NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH3:31])=[CH:15][CH:16]=2)[N:20]=[C:21]([C:27]([F:29])([F:30])[F:28])[CH:22]=1)=[O:25]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 812922-MethoxybenzylamineHCID 69298544HCID 69298544, compound

Product 1

HCID 69097944(S)-tert-butyl 1-((5-(5-(2-methoxybenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamateYield 24.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 25 (0.059 g, 0.128 mmol) in pyridine (0.851 mL) at 0° C. was added 2-methoxybenzylamine (0.020 mL, 0.153 mmol) and followed by dropwise addition of POCl3 (0.013 mL, 0.140 mmol). The mixture was stirred for 30 min at 0° C., then for 1 h from 0° C. to 21° C., then for 16 h at room temperature. The mixture was quenched with water and extracted with ethyl acetate, washed with brine, dried (MgSO4) filtered and concentrated. The residue was purified by silica gel column chromatography with gradient of EtOAc (20-60%) in hexanes to afford 26e (18 mg, 24%) as a white solid. LRMS (ESI): calc. 581.2; found 604.3 (MNa)+.

Workup

  1. waitfor 1 h from 0° C. to 21° C.
  2. waitfor 16 h at room temperature
  3. customThe mixture was quenched with water
  4. extractionextracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography with gradient of EtOAc (20-60%) in hexanes

Sources & evidence

ORD record
ord-e7d1362089354254b629f80a61d06067
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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