Hydrazine hydrate (1:1) → HCID 90011255, compound

HRID 1481478Notes

Reaction equation

HRID 1481478 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:14]([F:17])([F:16])[F:15])(O)[CH2:11][C:10]([C:18]3[O:19][CH:20]=CC=3)=[N:9]2)=[N:6][CH:7]=1.FC(F)(F)C(=O)C=C(C1OC=CC=1)OC.BrC1C=C[C:42]([NH:45][NH2:46])=NC=1.BrC1C=CC(Br)=CN=1.[OH2:55].NN>C(Cl)(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:14]([F:15])([F:16])[F:17])=[CH:11][C:10]([C:18]3[O:19][C:20](=[O:55])[N:45]([CH3:42])[N:46]=3)=[N:9]2)=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 24654Hydrazine hydrate (1:1)HCID 693532,5-DibromopyridineHCID 115356995-Bromo-2-hydrazinopyridineHCID 77984937HCID 77984937, compoundHCID 90011520HCID 90011520, compound

Product 1

HCID 90011255HCID 90011255, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

Step-1: 1-(5-Bromopyridin-2-yl)-3-(furan-2-yl)-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol: To a stirred solution of 1,1,1-trifluoro-4-(furan-2-yl)-4-methoxybut-3-en-2-one (129 g, 585 mmol; prepared by following the procedure described in Tett Lett., 2002, 43, 8701) in chloroform (600 mL) was added solid 5-bromo-2-hydrazinylpyridine (prepared by the reaction of 2,5-dibromopyridine with hydrazine hydrate, 110.0 g, 585 mmol) in 10 portions at 0° C. over a period of 30 min. The reaction was stirred for 1 h at room temperature, and then at 50° C. for 36 h. The reaction was cooled to 0° C. before the addition of water (200 mL) and chloroform (500 mL). The layers were separated and the aqueous layer was extracted with chloroform (3×200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (5% ethyl acetate-hexanes system as eluent) to afford 90 g (40%) of the title compound as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.17 (d, J=2.5 Hz, 1H), 7.96 (s, 1H, D2O Exchangeable), 7.75 (dd, J=2.5 & 8.5 Hz, 1H), 7.56 (d, J=1.5 Hz, 1H), 7.41(d, J=8.5 Hz, 1H), 6.76 (d, J=2.5 Hz, 1H), 6.54 (dd, J=1.5 & 2.5 Hz, 1H), 3.71(d, J=18.5 Hz, 1H), 3.56 (d, J=18.5 Hz, 1H); ESI-MS (m/z) 376, 378 [(MH)+, Br79,81].

Workup

  1. customprepared
  2. waitat 50° C. for 36 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with chloroform (3×200 mL)
  5. washThe combined organic layers were washed with brine (200 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customThe filtrate was rotary evaporated
  9. customthe crude product was purified by flash column chromatography (5% ethyl acetate-hexanes system as eluent)

Sources & evidence

ORD record
ord-3e94e2896d5247f38dfa43403d6a719e
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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