Azide → HCID 86696504, compound

HRID 1615905Notes

Reaction equation

HRID 1615905 reaction equation
[N:1]([C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[C:8]([NH:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:7]=[CH:6][N:5]=1)=[N+]=[N-].CP(C)C.[N-]=[N+]=[N-]>O1CCCC1.O>[C:18]1([CH2:17][CH2:16][CH2:15][NH:14][C:8]2[CH:7]=[CH:6][N:5]=[C:4]([NH2:1])[C:9]=2[C:10]([F:13])([F:11])[F:12])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 33558AzideHCID 68983Trimethylphosphine3×HCID 86696505HCID 86696505, compound

Product 1

HCID 86696504HCID 86696504, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-azido-N-(3-phenylpropyl)-3-(trifluoromethyl)pyridin-4-amine (125 mg, 0.389 mmol) in tetrahydrofuran (4.0 mL) and water (0.066 mL, 3.69 mmol was added trimethylphosphine (1.0 M in tetrahydrofuran; 0.443 mL, 0.443 mmol. After four hours starting material remained and an additional 500 μL of trimethylphosphine was added. After 21 hours, LC/MS showed a 6.7:1 ratio of desired:starting material. An additional 200 μL of trimethylphosphine was added. After 25 hours the ratio by LC/MS was 12:1 product:starting material. After 27 hours the mixture was concentrated. This material was purified on silica gel (12 g) equilibrated in hexane, loaded in dichloromethane and eluted using hexane (96 mL), 20% EtOAc/hexane (250 mL), 20 to 50% EtOAc/hexane (320 mL, linear gradient). Fractions 39-50 gave 84.5 mg of an off white crystalline solid. This was consistent with desired product by 1H NMR containing 10% of the starting azide. The material was used as is. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.79 (d, J=6.0 Hz, 1H), 7.39-7.29 (m, 2H), 7.25-7.15 (m, 3H), 5.98 (d, J=6.0 Hz, 1H), 4.96 (br. s., 3H), 3.25-3.12 (m, 2H), 2.73 (t, J=7.5 Hz, 2H), 1.98 (quin, J=7.3 Hz, 2H).

Workup

  1. waitAfter 21 hours
  2. waitAfter 25 hours the ratio by LC/MS was
  3. concentrationAfter 27 hours the mixture was concentrated
  4. customThis material was purified on silica gel (12 g)
  5. washeluted
  6. customFractions 39-50 gave 84.5 mg of an off white crystalline solid

Sources & evidence

ORD record
ord-7ac74b58438d40b4ae9b70b3fb8ed9c2
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

Loading…