Triphenylphosphine → HCID 86700915, compound

HRID 625133Notes

Reaction equation

HRID 625133 reaction equation
[CH3:1][O:2][C:3]1[S:7][C:6]2=[N:8][C:9]([C:11]3[O:12][C:13]4[C:14](=[C:16]([OH:20])[CH:17]=[CH:18][CH:19]=4)[CH:15]=3)=[CH:10][N:5]2[N:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:40]1([C:46]2[S:47][CH:48]=[C:49]([CH2:51]O)[N:50]=2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH3:1][O:2][C:3]1[S:7][C:6]2=[N:8][C:9]([C:11]3[O:12][C:13]4[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:51][C:49]5[N:50]=[C:46]([C:40]6[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=6)[S:47][CH:48]=5)[C:14]=4[CH:15]=3)=[CH:10][N:5]2[N:4]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 27764734-(Hydroxymethyl)-2-phenyl-1,3-thiazoleHCID 72201855HCID 72201855, compound

Product 1

HCID 86700915HCID 86700915, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2 °C

Procedure

A mixture of 2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (Example 38G, 0.100 g, 0.349 mmol), triphenylphosphine (0.165 g, 0.627 mmol) and (2-phenylthiazol-4-yl)methanol (Example 3B, 0.080 g, 0.418 mmol) in a 50 ml flask was maintained under vacuum for 10 min and then purged with nitrogen. Dry tetrahydrofuran (10 mL) was added and the resulting mixture was slightly warmed and maintained in an ultrasonic bath for 5 min. The cooled mixture (still heterogeneous) was treated at 22° C. with a solution of diisopropyl azodicarboxylate (0.113 g, 0.558 mmol) in tetrahydrofuran (2 mL) added dropwise over 1 h. The mixture was then stirred at 2° C. for 4 h. The clear reaction mixture was quenched by the addition of dichloromethane (100 mL) and saturated sodium bicarbonate (10 mL). The organic phase was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. Chromatography of the residue on silica gel (2.5×12 cm, elution dichloromethane-ethyl acetate 0-3%) followed by crystallization of the desired fraction from ethyl acetate (8 mL) gave 0.028 g (24% yield) of the title material as a white solid. LC (Method A): 2.426 min. HRMS (ESI) calcd for C23H17N4O3S2 [M+H]+ m/z 461.0737, found 461.0926. 1H NMR (CDCl3, 400 MHz) δ ppm: 4.22 (s, 3H), 5.45 (d, J=0.78 Hz, 2H), 6.80 (dd, J=7.04, 1.57 Hz, 1H), 7.15-7.21 (m, 2H), 7.22 (s, 1H), 7.38 (s, 1H), 7.42-7.51 (m, 3H), 7.92 (s, 1H), 7.95-8.03 (m, 2H).

Workup

  1. temperaturewas maintained under vacuum for 10 min
  2. custompurged with nitrogen
  3. additionDry tetrahydrofuran (10 mL) was added
  4. temperaturethe resulting mixture was slightly warmed
  5. temperaturemaintained in an ultrasonic bath for 5 min
  6. additionadded dropwise over 1 h
  7. customThe clear reaction mixture was quenched by the addition of dichloromethane (100 mL) and saturated sodium bicarbonate (10 mL)
  8. washThe organic phase was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customChromatography of the residue on silica gel (2.5×12 cm, elution dichloromethane-ethyl acetate 0-3%) followed by crystallization of the desired fraction from ethyl acetate (8 mL)

Sources & evidence

ORD record
ord-82916fa862574dc69d4f04398c1da7b5
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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