Acetohydrazide → HCID 66683024, compound

HRID 1964610Notes

Reaction equation

HRID 1964610 reaction equation
[N:1]1([C:5]([C:7]2[CH:33]=[CH:32][C:10]([O:11][C:12]3[CH:13]=[C:14]([C:24]4[NH:28][C:27]([C:29](O)=[O:30])=[CH:26][CH:25]=4)[CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=3)=[C:9]([F:34])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[C:35]([NH:38][NH2:39])(=[O:37])[CH3:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[C:35]([NH:38][NH:39][C:29]([C:27]1[NH:28][C:24]([C:14]2[CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=[C:12]([O:11][C:10]3[CH:32]=[CH:33][C:7]([C:5]([N:1]4[CH2:2][CH2:3][CH2:4]4)=[O:6])=[CH:8][C:9]=3[F:34])[CH:13]=2)=[CH:25][CH:26]=1)=[O:30])(=[O:37])[CH3:36]

Participants

6

Reactant 4

HCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66680966HCID 66680966, compound

Product 1

HCID 66683024HCID 66683024, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-{3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrole-2-carboxylic acid (126 mg, 0.27 mmol) synthesized in Example (66g) and acetohydrazide (40 mg, 0.54 mmol) were dissolved in dichloromethane (5 mL), and HATU (153 mg, 0.40 mmol) and N,N-diisopropylethylamine (70 μL, 0.40 mmol) were added at room temperature, followed by stirring under nitrogen atmosphere for 1 hour. The reaction solution was diluted with dichloromethane (60 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/dichloromethane=5%) to afford the desired product (87 mg, yield 62%) as a white solid.

Workup

  1. washwashed with 1N hydrochloric acid
  2. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified
  5. washsilica gel column chromatography (elution solvent: methanol/dichloromethane=5%)

Sources & evidence

ORD record
ord-dba1d4f656664702a1c6f21a222fa8fe
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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