Hydrochloric Acid → HCID 68756556, compound

HRID 1615213Notes

Reaction equation

HRID 1615213 reaction equation
Br[CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.P(OC)(OC)OC.C(O[K])(C)(C)C.[CH:26]([C:28]1[C:36]2[C:31](=[CH:32][C:33]([C:37]#[N:38])=[CH:34][CH:35]=2)[NH:30][N:29]=1)=O.Cl>CN(C=O)C.O>[C:37]([C:33]1[CH:32]=[C:31]2[C:36]([C:28](/[CH:26]=[CH:2]/[C:3]3[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=3)=[N:29][NH:30]2)=[CH:35][CH:34]=1)#[N:38]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8472Trimethyl phosphiteHCID 256687Methyl 4-(bromomethyl)benzoateHCID 178418922HCID 178418922, compoundHCID 178509486HCID 178509486, compound

Product 1

HCID 68756556HCID 68756556, compoundYield 104.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
125 °C

Procedure

A mixture of methyl 4-(bromomethyl)benzoate (4.58 g, 20 mmol) and trimethyl phosphite (3.54 mL, 30 mmol) was refluxed (oil temp. 125° C.) for 1 h under argon. After cooling to rt, the reaction mixture was diluted with DMF (50 mL) and cooled to 0° C. using ice bath. tBuOK (3.92 g, 35 mmol) was added slowly. After addition, the resulting dark brown solution was stirred for 5 min at 0° C. before a solution of 3-formyl-1H-indazole-6-carbonitrile (2.0 g, 11.7 mmol) in DMF (15 mL) was added dropwise via a pasteur pipette over 5 min. The reaction mixture was then stirred for 90 min at 0° C.; 2N HCl (25 mL) was added slowly over 2 min, followed by H2O (100 mL). The resulting suspension was stirred for 5 min at 0° C. The precipiates collected by suction filtration were rinsed well with H2O and dried to give crude (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (3.70 g) as an orange solid. Trituration with 50 mL of ether, followed by sonication and suction filtration gave pure (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (2.56 g, 72%) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ 13.83 (s, 1H), 8.43 (d, J=8.8 Hz, 1H), 8.18 (s, 1H), 7.97 (d, J=8.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 2H), 7.76 (d, J=16.4 Hz, 1H), 7.63 (d, J=16.8 Hz, 1H), 7.55 (d, J=8.4 Hz, 1H), 3.86 (s, 3H); MS ESI 304.1 [M+H]+, calcd for [C18H13N3O2+H]+ 304.1.

Workup

  1. temperatureAfter cooling to rt
  2. temperaturecooled to 0° C.
  3. additionAfter addition
  4. additionwas added dropwise via a pasteur pipette over 5 min
  5. stirringThe resulting suspension was stirred for 5 min at 0° C
  6. filtrationThe precipiates collected by suction filtration
  7. washwere rinsed well with H2O
  8. customdried

Sources & evidence

ORD record
ord-9a6b4e7fc600446bbdb1bf9402dfcf48
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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