Ethanol → HCID 178422797, compound

HRID 73734Notes

Reaction equation

HRID 73734 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26](/[CH:27]=[CH:28]/[C:29](=O)[CH3:30])=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1.C1(C)C=CC(S([NH:41][NH2:42])(=O)=O)=CC=1.CCO.C[O-].[Na+]>C(O)=O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[NH:42][N:41]=[C:29]([CH3:30])[CH:28]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 702EthanolHCID 15303P-ToluenesulfonylhydrazideHCID 10942334Sodium MethoxideHCID 86702596(R,E)-6-(3-Hydroxypyrrolidin-1-yl)-5-(3-oxobut-1-en-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 178422797HCID 178422797, compound

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
80 °C

Procedure

(R,E)-6-(3-Hydroxypyrrolidin-1-yl)-5-(3-oxobut-1-en-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 3.1, 50 mg, 0.091 mmol) and toluene-4-sulfonic acid hydrazide (34.5 mg, 0.181 mmol) and EtOH (302 μL) were added to a MW vial, which was sealed and stirred at 80° C. for 1.5 h. The mixture was cooled to RT, NaOMe (17.15 mg, 0.318 mmol) was added and the RM was stirred at 80° C. for 48 h. Aq. The RM was acidified with aq. formic acid, filtered through a 0.2 μM PTFE membrane filter and purified by preparative HPLC (Condition 9, from 20% to 50% in 18 min) to yield the title compound as a white solid. UPLC-MS (Condition 1) tR=2.08 min, m/z=448.0 [M+H]+, m/z=446.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.79 (m, 1H) 1.78-1.90 (m, 1H) 2.29 (br. s, 3H) 2.98 (d, J=11.74 Hz, 1H) 3.25-3.37 (m, 2H) 3.40-3.53 (m, 1H) 4.21 (br. s, 1H) 4.83 (br. s, 1H) 6.13 (s, 1H) 7.33 (d, J=8.31 Hz, 2H) 7.86 (d, 2H) 8.01 (br. s, 1H) 8.71 (br. s, 1H) 10.15 (s, 1H) 12.57 (br. s, 1H).

Workup

  1. customwas sealed
  2. temperatureThe mixture was cooled to RT
  3. stirringthe RM was stirred at 80° C. for 48 h
  4. filtrationfiltered through a 0.2 μM PTFE membrane
  5. filtrationfilter
  6. custompurified by preparative HPLC (Condition 9, from 20% to 50% in 18 min)

Sources & evidence

ORD record
ord-a6b97eec55354f5194c692e3eaf04c39
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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