Acetohydrazide → HCID 67111050, compound

HRID 540771Notes

Reaction equation

HRID 540771 reaction equation
C(N(C(C)C)CC)(C)C.[CH2:10]([N:12]1[C:16]([O:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=2)=[CH:15][C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([NH:36][S:37]([CH2:40][C:41]([F:44])([F:43])[F:42])(=[O:39])=[O:38])([CH3:35])[CH3:34])[CH:28]=2)=[N:13]1)[CH3:11].[C:45]([NH:48][NH2:49])(=[O:47])[CH3:46]>CN(C=O)C>[C:45]([NH:48][NH:49][C:22]([C:21]1[CH:25]=[CH:26][C:18]([O:17][C:16]2[N:12]([CH2:10][CH3:11])[N:13]=[C:14]([C:27]3[CH:28]=[C:29]([C:33]([NH:36][S:37]([CH2:40][C:41]([F:42])([F:44])[F:43])(=[O:39])=[O:38])([CH3:34])[CH3:35])[CH:30]=[CH:31][CH:32]=3)[CH:15]=2)=[CH:19][CH:20]=1)=[O:24])(=[O:47])[CH3:46]

Participants

5

Reactant 3

HCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 69932982HCID 69932982, compound

Product 1

HCID 67111050HCID 67111050, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

(1-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (161 mg, 0.36 mmol, 1.2 equiv) and diisopropylethylamine (117 mg, 0.91 mmol, 3 equiv) were added to a stirring solution of 4-({1-ethyl-3-[3-(2-{[(2,2,2-trifluoroethyl)sulfonyl]amino}propan-2-yl)phenyl]-1H-pyrazol-5-yl}oxy)benzoic acid (155 mg, 0.30 mmol, 1 equiv) in DMF (3 mL). Acetohydrazide (45 mg, 0.61 mmol, 2 equiv) was then added and the mixture was stirred at 22° C. for 16 hours. The mixture was purified directly by reversed phase HPLC (0-95% acetonitrile:water with 0.025% TFA). Pure fractions were identified, combined, and lyophilized to give N-{2-[3-(5-{4-[(2-acetylhydrazinyl)carbonyl]phenoxy}-1-ethyl-1H-pyrazol-3-yl)phenyl]propan-2-yl}-2,2,2-trifluoroethanesulfonamide (35% yield). This material was stirred in THF (1 mL) at 22° C. and 3,3,3-triethyl-1-(methoxycarbonyl)diazathian-3-ium-1-ide 2,2-dioxide (38 mg, 0.16 mmol, 1.5 equiv) was added. The resulting mixture was stirred at 22° C. for 16 hours then purified directly by reversed phase HPLC (0-95% acetonitrile:water with 0.025% TFA). Pure fractions were identified, combined, and lyophilized to give the title compound (21% yield). Calc'd (M+1)+: 550.2. Found: 550.1.

Workup

  1. customThe mixture was purified directly by reversed phase HPLC (0-95% acetonitrile:water with 0.025% TFA)

Sources & evidence

ORD record
ord-a8e3a041a94c47d4a8ed0831c0246b36
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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