Acetic Acid → 7-(2-{[5-(1-Ethyl-1-hydroxypropyl)-1,3,4-thiadiazol-2-yl]amino}ethyl)-4-(4-fluorophenyl)-2H-chromen-2-one

HRID 1988198Notes

Reaction equation

HRID 1988198 reaction equation
[NH2:1][C:2]1[S:6][C:5]([C:7]([OH:12])([CH2:10][CH3:11])[CH2:8][CH3:9])=[N:4][N:3]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]3[C:24](=[CH:25][C:26]([CH:30]=O)=[CH:27][CH:28]=3)[O:23][C:22](=[O:32])[CH:21]=2)=[CH:16][CH:15]=1.[C:33](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1C=CC=CC=1.C1COCC1>[CH2:8]([C:7]([C:5]1[S:6][C:2]([NH:1][CH2:33][CH2:30][C:26]2[CH:25]=[C:24]3[C:29]([C:20]([C:17]4[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=4)=[CH:21][C:22](=[O:32])[O:23]3)=[CH:28][CH:27]=2)=[N:3][N:4]=1)([OH:12])[CH2:10][CH3:11])[CH3:9]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 468452294-(4-Fluorophenyl)-2-oxo-2H-chromene-7-carbaldehydeHCID 574378443-(5-Amino-1,3,4-thiadiazol-2-yl)pentan-3-ol

Product 1

HCID 866133337-(2-{[5-(1-Ethyl-1-hydroxypropyl)-1,3,4-thiadiazol-2-yl]amino}ethyl)-4-(4-fluorophenyl)-2H-chromen-2-one

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(5-amino-1,3,4-thiadiazol-2-yl)pentan-3-ol (0.129 g, 0.689 mmol), 4-(4-fluorophenyl)-2-oxo-2H-chromene-7-carbaldehyde (0.200 g, 0.746 mmol) and acetic acid (7.94 μL, 0.138 mmol) in benzene (2.5 mL) was stirred overnight at reflux with a Dean-Stark trap. After cooling, the mixture was diluted in THF (5 mL) and sodium triacetoxyborohydride (0.731 g, 3.45 mmol) was added. The mixture was then stirred at 45° C. for 3 h. The reaction was quenched with a saturated NaHCO3 solution and portioned between EtOAc and water. The organic layer was dried over MgSO4, filtered and concentrated. The crude residue obtained was purified by column chromatography (Hexane-EtOAc-MeOH, 50:50:0 to 0:98:2) to yield the title compound. 1H NMR (400 MHz, acetone-d6): δ 8.7 (m, 2H), 7.5 (s, 1H), 7.45 (s, 1H), 7.4 (m, 3H), 6.35 (s, 1H), 4.75 (s, 2H), 4.5 (bs, 1H), 2.0-1.75 (m, 4H), 0.9 (t, 6H).

Workup

  1. temperatureat reflux with a Dean-Stark trap
  2. temperatureAfter cooling
  3. stirringThe mixture was then stirred at 45° C. for 3 h
  4. customThe reaction was quenched with a saturated NaHCO3 solution
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue obtained
  9. customwas purified by column chromatography (Hexane-EtOAc-MeOH, 50:50:0 to 0:98:2)

Sources & evidence

ORD record
ord-f7b5174f9a1e4a92b8d0971b2b19d8ba
Source dataset
uspto-grants-2009_06
Patent number
US07553973B2

Reaction notes

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