Dichloromethane → HCID 57950500, compound

HRID 598868Notes

Reaction equation

HRID 598868 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][N:7]=[CH:6]2)#[CH:2].[N:12]([CH2:15][CH2:16][C@@H:17]([NH:29]C(=O)OC(C)(C)C)[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)=[N+:13]=[N-:14].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].C(Cl)Cl>CC(O)(C)C.O>[NH:8]1[C:9]2[C:5](=[CH:4][C:3]([C:1]3[N:14]=[N:13][N:12]([CH2:15][CH2:16][C@@H:17]([NH2:29])[CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][CH:20]=4)[CH:2]=3)=[CH:11][CH:10]=2)[CH:6]=[N:7]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 178424335-ethynyl-1H-indazoleHCID 23667548Sodium AscorbateHCID 86635695HCID 86635695, compound

Product 1

HCID 57950500HCID 57950500, compoundYield 2.9%

Reagents, catalysts & solvents 1

HCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

5-Ethynyl-1H-indazole (50 mg, 0.35 mmol) and (S)-tert-butyl 4-azido-1-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate (143 mg, 0.35 mmol) were dissolved in 2 mL tBuOH/H2O (1/1) and CuSO4.5H2O (1.8 mg, 0.007 mmol) and sodium ascorbate (14 mg, 0.07 mmol) were added. The reaction was stirred for 3 days at room temperature and 10 mL DCM was added and the phases were separated. The aqueous phase was extracted with 50 mL DCM (3×50 mL) and the combined organic phases were dried over MgSO4 and evaporated. The BOC protected intermediate was purified on preparative TLC (6% MeOH in DCM) and treated with 4 mL 30% TFA in DCM for 2 hours. Toluene (30 mL) was added and the mixture was evaporated. The residue was redissolved in 2 mL MeOH, 3 drops of NaOH (5 M, aqueous) was added, and the solution was applied onto a preparative TLC plate for purification (10% MeOH in DCM). 4 mg of the title compound was obtained (0.01 mmol) as a colorless film. LCMS (API-ES) m/z (%): 401.0 (100%, M++H); 1H NMR (300 MHz, CD3OD) δ ppm 8.25-8.30 (m, 1H), 8.17-8.22 (m, 1H), 8.06-8.11 (m, 1H), 7.85 (dd, J=8.76, 1.60 Hz, 1H), 7.54-7.64 (m, 3H), 7.39 (d, J=8.10 Hz, 2H), 4.61 (t, J=7.35 Hz, 2H), 2.98-3.11 (m, 1H), 2.85-2.97 (m, 1H), 2.72-2.83 (m, 1H), 2.06-2.22 (m, 1H), 1.87-2.05 (m, 1H).

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted with 50 mL DCM (3×50 mL)
  3. dry with materialthe combined organic phases were dried over MgSO4
  4. customevaporated
  5. customThe BOC protected intermediate was purified on preparative TLC (6% MeOH in DCM)
  6. additiontreated with 4 mL 30% TFA in DCM for 2 hours
  7. additionToluene (30 mL) was added
  8. customthe mixture was evaporated
  9. dissolutionThe residue was redissolved in 2 mL MeOH
  10. addition3 drops of NaOH (5 M, aqueous) was added
  11. customthe solution was applied onto a preparative TLC plate for purification (10% MeOH in DCM)

Sources & evidence

ORD record
ord-39a82393d24840dbb487c06b730f6103
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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