Triphenylphosphine → HCID 66558918, compound

HRID 1530579Notes

Reaction equation

HRID 1530579 reaction equation
C(OC(N1CC[CH:14]([CH:17]([O:20][C:21]2[CH:43]=[CH:42][C:24]3[C:25]4[N:29]([CH2:30][CH2:31][O:32][C:23]=3[CH:22]=2)[CH:28]=[C:27]([C:33]2[N:34]([CH:39]([CH3:41])[CH3:40])[N:35]=[C:36]([CH3:38])[N:37]=2)[N:26]=4)[CH2:18]C)CC1)=O)C1C=CC=CC=1.[CH3:44][C:45]1[S:46][C:47](C(O)C)=[C:48](C)[N:49]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCOCC1>[CH3:44][C:45]1[S:46][C:14]([CH:17]([O:20][C:21]2[CH:43]=[CH:42][C:24]3[C:25]4[N:29]([CH:28]=[C:27]([C:33]5[N:34]([CH:39]([CH3:40])[CH3:41])[N:35]=[C:36]([CH3:38])[N:37]=5)[N:26]=4)[CH2:30][CH2:31][O:32][C:23]=3[CH:22]=2)[CH3:18])=[C:48]([CH3:47])[N:49]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 5462977Diethyl azodicarboxylate2×HCID 45792553HCID 45792553, compound2×HCID 68312705HCID 68312705, compound

Product 1

HCID 66558918HCID 66558918, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (345 mg, 1.06 mmol), 1-(2,4-dimethylthiazol-5-yl)ethanol (250 mg, 1.59 mmol) and triphenylphosphine (0.84 g, 3.18 mmol) in dioxane (15 mL) was added dropwise DEAD (0.63 mL, 3.18 mmol) and the reaction mixture was stirred at RT for 18 h. Additional amounts of 1-(2,4-dimethylthiazol-5-yl)ethanol (100 mg, 0.63 mmol) and triphenylphosphine (0.42 g, 1.59 mmol) were added, followed by DEAD (0.31 mL, 1.59 mmol) and stirring at RT was continued for 72 h. Volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was further purified by column chromatography (Si-PCC, gradient 0-6% MeOH in EtOAc then C18, gradient 15-70% MeOH in H2O) and finally loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH affording 188 as a white solid (60 mg, 12%). LCMS: RT 4.42 min [M+H]+ 465.1. 1H NMR (CDCl3, 400 MHz): δ 8.33 (1H, d, J=9.33 Hz), 7.53 (1H, s), 6.65 (1H, dd, J=9.33 and 2.56 Hz), 6.46 (1H, d, J=2.71), 5.91-5.81 (1H, m), 5.54-5.48 (1H, m), 4.44-4.29 (4H, m), 2.57 (3H, s), 2.39 (3H, s), 2.37 (3H, s), 1.65 (3H, d J=6.22 Hz), 1.52 (6H, d, J=6.72 Hz)

Workup

  1. stirringstirring at RT
  2. waitwas continued for 72 h
  3. customVolatiles were removed under reduced pressure
  4. washwas washed with MeOH
  5. washthe product eluted with 2M NH3/MeOH
  6. additionThe product containing fractions
  7. concentrationconcentrated in vacuo
  8. customthe resulting residue was further purified by column chromatography (Si-PCC, gradient 0-6% MeOH in EtOAc
  9. washThe cartridge was washed with MeOH
  10. washthe product eluted with 2M NH3/MeOH affording 188 as a white solid (60 mg, 12%)

Sources & evidence

ORD record
ord-28c9fa078af0451cbaa507a6f3a71277
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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