Formic Acid → HCID 11855331, compound

HRID 736755Notes

Reaction equation

HRID 736755 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH:23][CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH:25]3[C:30](O)=[O:31])(=[O:22])=[O:21])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH:33][N:34]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.NO.[CH:57](O)=[O:58]>CN(C=O)C>[OH:33][NH:34][C:30]([C@@H:25]1[C@H:24]([NH:23][S:20]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH2:12][C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]([CH3:1])[CH:11]=3)=[CH:15][CH:16]=2)(=[O:22])=[O:21])[CH2:29][CH2:28][N:27]([CH:57]=[O:58])[CH2:26]1)=[O:31]

Participants

7

Reactant 5

HCID 284Formic AcidHCID 787HydroxylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68817351HCID 68817351, compound

Product 1

HCID 11855331HCID 11855331, compoundYield 11.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-piperidine-3-carboxylic acid (0.210 g, 0.459 mmol) and 1-hydroxybenzotriazole (HOBT, 0.186 g, 1.38 mmol) in DMF (10 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.264 g, 1.38 mmol) at 0° C. The reaction mixture stirred at 0° C. for 10 min, then warmed to 25° C. over 1.0 h. After re-cooling the reaction to 0° C., hydroxylamine (50% by wt in water solution, 0.5 mL, 4.6 mmol) was added. The reaction was allowed to warm to 25° C. over 19 h and then formic acid (0.151 g, 3.2 mmol) added. The reaction was stirred for 10 min at 25° C. and 40° C. for 30 min and then allowed to warm to 25° C. over 19 h. The DMF was removed in vacuo and the resulting oil was diluted in ethyl acetate (100 mL) and then washed with saturated aqueous sodium bicarbonate (3×30 mL) and brine (30 mL). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude solid (0.195 g). The crude product was purified by reverse phase HPLC (Gilson) on a Phenomex C-18 semi-prep column eluting with an acetonitrile:water gradient, to afford (3S,4R)-1 -formyl-4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonyl amino]-piperidine-3-carboxylic acid hydroxyamide as an amorphous white solid (0.025 g, 11.6%). MS: 499 (M+H)+

Workup

  1. temperaturewarmed to 25° C. over 1.0 h
  2. temperatureAfter re-cooling
  3. customthe reaction to 0° C.
  4. temperatureto warm to 25° C. over 19 h
  5. stirringThe reaction was stirred for 10 min at 25° C. and 40° C. for 30 min
  6. temperatureto warm to 25° C. over 19 h
  7. customThe DMF was removed in vacuo
  8. additionthe resulting oil was diluted in ethyl acetate (100 mL)
  9. washwashed with saturated aqueous sodium bicarbonate (3×30 mL) and brine (30 mL)
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto obtain a crude solid (0.195 g)
  14. customThe crude product was purified by reverse phase HPLC (Gilson) on a Phenomex C-18 semi-prep column
  15. washeluting with an acetonitrile

Sources & evidence

ORD record
ord-26663a3b2f104f7b911d2993898c330d
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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