Triethylamine → HCID 44251363, compound

HRID 658973Notes

Reaction equation

HRID 658973 reaction equation
[NH2:1][C@@H:2]1[CH2:8][CH2:7][C@@H:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=2[F:16])[CH2:5][N:4]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:3]1=[O:22].Cl[C:24](OC1C=CC([N+]([O-])=O)=CC=1)=[O:25].C(N(CC)CC)C.FC(F)(F)C(O)=O.[CH3:50][N:51]1[C:55]2=[N:56][CH:57]=[CH:58][CH:59]=[C:54]2[N:53]([CH:60]2[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)[C:52]1=[O:66]>C1COCC1.C(Cl)(Cl)Cl>[F:16][C:10]1[C:11]([F:15])=[CH:12][CH:13]=[CH:14][C:9]=1[C@H:6]1[CH2:5][N:4]([CH2:17][C:18]([F:21])([F:19])[F:20])[C:3](=[O:22])[C@H:2]([NH:1][C:24]([N:63]2[CH2:64][CH2:65][CH:60]([N:53]3[C:54]4[C:55](=[N:56][CH:57]=[CH:58][CH:59]=4)[N:51]([CH3:50])[C:52]3=[O:66])[CH2:61][CH2:62]2)=[O:25])[CH2:8][CH2:7]1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 23653826(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-oneHCID 68777582HCID 68777582, compound

Product 1

HCID 44251363HCID 44251363, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one [Burgey et al. U.S. Pat. No. 6,953,790 B2] (16 mg, 0.050 mmol) in THF (8 mL) at 0° C. was added 4-nitrophenyl chloroformate (11 mg, 0.055 mmol) and triethylamine (0.015 mL, 0.11 mmol) and the resulting mixture was stirred at 0° C. for 1 h. A solution of 3-methyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one trifluoroacetate from Step C (34 mg, 0.074 mmol) and triethylamine (0.042 mL, 0.30 mmol) in CHCl3 (8 mL) was added and the resulting mixture was stirred at ambient temperature for 18 h then concentrated under reduced pressure. The residue was partitioned between CH2Cl2 (20 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 95:5, to give the title compound. MS: m/z=581 (M+1). HRMS: m/z=581.2265; calculated m/z=581.2294 for C27H30F5N6O3.

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature for 18 h
  2. concentrationthen concentrated under reduced pressure
  3. customThe residue was partitioned between CH2Cl2 (20 mL) and saturated aqueous NaHCO3 (10 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-a1378974c52d4923a056e9812036f952
Source dataset
uspto-grants-2011_12
Patent number
US08080544B2

Reaction notes

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