Methanol → HCID 86700903, compound

HRID 1424360Notes

Reaction equation

HRID 1424360 reaction equation
Br[C:2]1[S:6][C:5]2=[N:7][C:8]([C:10]3[O:11][C:12]4[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([O:20][CH2:21][C:22]5[N:23]=[C:24]([C:27]6[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=6)[S:25][CH:26]=5)[C:13]=4[CH:14]=3)=[CH:9][N:4]2[N:3]=1.[CH3:33][OH:34].C[O-].[Na+]>ClCCl>[F:19][C:17]1[CH:16]=[C:15]([O:20][CH2:21][C:22]2[N:23]=[C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[S:25][CH:26]=2)[C:13]2[CH:14]=[C:10]([C:8]3[N:7]=[C:5]4[N:4]([CH:9]=3)[N:3]=[C:2]([O:34][CH3:33])[S:6]4)[O:11][C:12]=2[CH:18]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 86700901HCID 86700901, compound

Product 1

HCID 86700903HCID 86700903, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Bromo-6-(6-fluoro-4-((2-phenylthiazol-4-yl)methoxy)benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (17 mgs, 0.032 mmol) was dissolved in dichloromethane (1.3 mL) (some heat and sonication were required). Methanol was then added (0.3 mL) followed by sodium methoxide (14.74 μL, 0.064 mmol) in one shot. The reaction was stirred at r.t. for 25 min., then quenched with HCl 1.0 N and stirred until the reaction color changes to yellow. Sat. NaHCO3 was then added and this was extracted with dichloromethane (4×). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by silica gel column chromatography (BIOTAGE® 12 g column using 100% dichloromethane to 5% ethyl acetate in dichloromethane (increment of 1%) to give the title material (10 mgs, 64%) as a yellowish solid. LC (Method A): 2.488 min. HRMS (ESI) calcd for C23H15FN4O3S2 [M+H]+ m/z 479.0570. found 479.0661. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94-8.03 (m, 2H), 7.89 (s, 1H), 7.43-7.53 (m, 3H), 7.39 (s, 1H), 7.19 (s, 1H), 6.85-6.94 (m, 1H), 6.59-6.68 (m, 1H), 5.40 (s, 2H), 4.23 (s, 3H).

Workup

  1. temperaturesome heat
  2. customsonication
  3. customquenched with HCl 1.0 N
  4. stirringstirred until the reaction color changes to yellow
  5. additionSat. NaHCO3 was then added
  6. extractionthis was extracted with dichloromethane (4×)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (BIOTAGE® 12 g column

Sources & evidence

ORD record
ord-79f39d3a875140b4801645982a47a8a2
Source dataset
uspto-grants-2015_01
Patent number
US08927688B2

Reaction notes

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