Tetrahydrofuran → HCID 68759347, compound

HRID 1615215Notes

Reaction equation

HRID 1615215 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=3)=[N:8][NH:9]2)=[CH:5][CH:4]=1)#[N:2].[OH-].[Na+].C1COCC1>CO>[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]3[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)=[N:8][NH:9]2)=[CH:5][CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 68756556HCID 68756556, compound

Product 1

HCID 68759347HCID 68759347, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a round bottom flash containing (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (606 mg, 2 mmol) was added 2 M NaOH (20 mL, 40 mmol), followed by THF (10 mL) and MeOH (10 mL). The resulting mixture was stirred O/N at rt. After removal of THF and MeOH via rotavap, the residue was cooled to 0° C. and treated with 2 M HCl (25 mL) and stirred for 2 min at that temp. The precipitates collected by suction filtration were rinsed with H2O to give crude (E)-4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoic acid as a brown red solid. It was redissolved in HOAc/pyridine/DMF (4 mL/8 mL/6 mL) and a solution of NaH2PO2 (704 mg, 8 mmol) in H2O (4 mL) was added, followed by Raney-Nickel 2400 (slurry in H2O, 0.4 mL). The resulting mixture was heated for 1 h at 55° C. (oil temp.). Usual aqueous workup, followed by trituration with H2O gave the title compound (332 mg, 54%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 13.81 (s, 1H), 12.90 (s, br, 1H), 10.14 (s, 1H), 8.39 (d, J=8.0 Hz, 1H), 8.19 (s, 1H), 7.96 (d, J=8.0 Hz, 2H), 7.86 (d, J=8.0 Hz, 2H), 7.76 (d, J=16.8 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.64 (d, J=16.4 Hz, 1H); MS ESI 293.0 [M+H]+, calcd for [C17H12N2O3+H]+ 293.1.

Workup

  1. customAfter removal of THF and MeOH via rotavap
  2. temperaturethe residue was cooled to 0° C.
  3. additiontreated with 2 M HCl (25 mL)
  4. stirringstirred for 2 min at that temp
  5. filtrationThe precipitates collected by suction filtration
  6. washwere rinsed with H2O

Sources & evidence

ORD record
ord-6371c0455f484e95b8266bf0e040891c
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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