Anisole → HCID 59464296, compound

HRID 1713738Notes

Reaction equation

HRID 1713738 reaction equation
C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.O.[C:17]1([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:22]=[CH:21][CH:20]=[C:19]([N:23](COCC[Si](C)(C)C)[C:24]2[O:28][C:27]([C:29]([N:31]([C:40]3[CH:41]=[N:42][C:43]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:44][CH:45]=3)COCC[Si](C)(C)C)=[O:30])=[N:26][N:25]=2)[CH:18]=1>C(Cl)Cl>[C:17]1([C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][C:24]2[O:28][C:27]([C:29]([NH:31][C:40]3[CH:41]=[N:42][C:43]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:44][CH:45]=3)=[O:30])=[N:26][N:25]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 7519AnisoleHCID 22392675Trifluoroacetic acid waterHCID 59464060HCID 59464060, compound2×

Product 1

HCID 59464296HCID 59464296, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Anisole (0.14 mL, 1.30 mmol) and a mixture of TFA:water (9:1) (3 mL) was added to (5-(biphenyl-3-yl{[2-(trimethylsilyl)ethoxy]methyl}amino)-N-(6-morpholin-4-ylpyridin-3-yl)-N-{[2-(trimethylsilyl)ethoxy]methyl}-1,3,4-oxadiazole-2-carboxamide (Intermediate 49, 180 mg, 0.28 mmol). After 30 minutes the mixture was by diluted with DCM (40 mL) and washed with 1M aqueous NaHCO3 (20 mL). The DCM layer was separated and MeOH (5 mL) was added. The aqueous was again extracted with MeOH:DCM (1:9) (4×10 mL). DMF (5 mL) was added to the aqueous and the aqueous was extracted with MeOH:DCM (1:9) (2×10 mL). All organics were combined, dried, filtered and evaporated to give a solid which was triturated with hot Et2O (10 mL) and washed with Et2O (2×5 mL) then hexane (2×5 mL). Chromatography through silica using 0-100% DCM/EtOAc then 10% MeOH/DCM as eluent gave the title compound (30 mg, 24%) as a solid; 1H NMR δ 11.10 (1H, s), 10.98 (1H, s), 8.53 (1H, d), 7.99-0.93 (1H, m), 7.91 (1H, s), 77.67-7.61 (3H, m), 7.54-7.47 (3H, m), 7.41 (1H, t), 7.35 (1H, d), 6.88 (1H, d), 3.74-3.69), (4H, m), 3.45-3.40 (4H, m); MS m/e MH+ 443.

Workup

  1. washwashed with 1M aqueous NaHCO3 (20 mL)
  2. customThe DCM layer was separated
  3. additionMeOH (5 mL) was added
  4. extractionThe aqueous was again extracted with MeOH:DCM (1:9) (4×10 mL)
  5. additionDMF (5 mL) was added to the aqueous and the
  6. extractionaqueous was extracted with MeOH:DCM (1:9) (2×10 mL)
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customto give a solid which
  11. customwas triturated with hot Et2O (10 mL)
  12. washwashed with Et2O (2×5 mL)

Sources & evidence

ORD record
ord-53f2df4e693b4c5c90c9e035ac93cd97
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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