Sodium Methoxide → HCID 72201854, compound

HRID 625131Notes

Reaction equation

HRID 625131 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22](Br)[S:21]4)[O:17][C:13]=2[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][O-:28].[Na+]>ClCCl.CO>[CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22]([O:28][CH3:27])[S:21]4)[O:17][C:13]=2[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 86700914HCID 86700914, compound

Product 1

HCID 72201854HCID 72201854, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-(4-(benzyloxy)benzofuran-2-yl)-2-bromoimidazo[2,1-b][1,3,4]thiadiazole (Example 38E, 3.22 g, 7.55 mmol) in a mixture of dichloromethane (400 mL) and methanol (50 mL) was treated at 22° C. with 6.3 mL of a 25 wt. % solution of sodium methoxide in methanol (30.2 mmol) added in one portion. More methanol (45 mL) was added and the mixture was stirred for 40 min. The reaction mixture was quenched by the addition of 40 mL of 1 N hydrochloric acid followed by 10 ml of saturated sodium bicarbonate. The solvent was evaporated under reduced pressure and the residue was diluted with dichloromethane (400 mL), washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. Crystallization of the white solid residue from 1,2-dichloroethane (30 mL) gave 2.19 g of the title material as a white solid. Chromatography of the mother liquors on silica gel (3×10 cm, elution with dichloromethane-ethyl acetate 0-1%) gave another 0.46 g of product (total yield 2.65 g, 93%). LC (Method A): 2.379 min. HRMS (ESI) calcd for C20H16N3O3S [M+H]+ m/z 378.0907, found 378.0911. 1H NMR (CDCl3, 600 MHz) δ ppm: 4.18 (s, 3H), 5.21 (s, 2H), 6.71 (dd, J=7.4 Hz and J=0.95 Hz, 1H), 7.12-7.17 (m, 3H), 7.32 (broad t, 1H), 7.38 (broad t, 2H), 7.47 (broad d, 2H), 7.88 (s, 1H).

Workup

  1. additionadded in one portion
  2. customThe reaction mixture was quenched by the addition of 40 mL of 1 N hydrochloric acid
  3. customThe solvent was evaporated under reduced pressure
  4. additionthe residue was diluted with dichloromethane (400 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customCrystallization of the white solid residue from 1,2-dichloroethane (30 mL)

Sources & evidence

ORD record
ord-bf60497c16b648098399353f90b37536
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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