Methanol → HCID 67389224, compound

HRID 241572Notes

Reaction equation

HRID 241572 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@H:9]1[C@@H:14]([NH:15]C(=O)OC(C)(C)C)[CH2:13][C@@H:12]([N:23]2[CH2:28][CH2:27][N:26]3[N:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:31]=[C:25]3[CH2:24]2)[C:11](=O)[N:10]1[CH3:37].CO>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@H:9]1[C@@H:14]([NH2:15])[CH2:13][C@@H:12]([N:23]2[CH2:28][CH2:27][N:26]3[N:29]=[C:30]([C:32]([F:34])([F:33])[F:35])[N:31]=[C:25]3[CH2:24]2)[CH2:11][N:10]1[CH3:37]

Participants

4

Reactant 2

HCID 887MethanolHCID 86657488HCID 86657488, compound

Product 1

HCID 67389224HCID 67389224, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product from Step A (320 mg, 0.603 mmol) was partially dissolved in THF (20 mL) at room temperature. Borane-methyl sulfide complex (3.62 mL, 3.62 mmol) was added. The mixture was stirred at room temperature for 1 h, and then refluxed overnight. Borane-methyl sulfide complex (1.206 mL, 1.206 mmol) was added to the solution and the mixture was stirred at room temperature for 0.5 h, and then heated to (65-67° C.) for 6 h. Methanol (4 mL) was added with caution and the mixture was concentrated under reduced pressure. The residue was dissolved in n-PrOH (45 mL) and the solution was refluxed for overnight. The residue was purified by column chromatography on silica gel Biotage 25M™, eluting with EtOAc/CH2Cl2 (gradient from 0% to 60%) to give the desired product which was treated with 1:1 TFA/CH2Cl2 for 1 h. The residue was purified by preparative TLC on silica gel, eluting with CH2Cl2/MeOH/aqueous NH3 (90/9/1) to give the title compound. LC-MS: 416.91 (M+1).

Workup

  1. additionBorane-methyl sulfide complex (3.62 mL, 3.62 mmol) was added
  2. temperaturerefluxed overnight
  3. additionBorane-methyl sulfide complex (1.206 mL, 1.206 mmol) was added to the solution
  4. stirringthe mixture was stirred at room temperature for 0.5 h
  5. temperatureheated to (65-67° C.) for 6 h
  6. concentrationthe mixture was concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in n-PrOH (45 mL)
  8. temperaturethe solution was refluxed for overnight
  9. customThe residue was purified by column chromatography on silica gel Biotage 25M™
  10. washeluting with EtOAc/CH2Cl2 (gradient from 0% to 60%)

Sources & evidence

ORD record
ord-59de82edcb6a40ffb0e524fce67ec830
Source dataset
uspto-grants-2014_02
Patent number
US08653059B2

Reaction notes

Loading…