Triphenylphosphine → HCID 117739744, compound

HRID 928622Notes

Reaction equation

HRID 928622 reaction equation
CS(O[CH2:6][CH2:7][O:8][CH2:9][CH:10]1[CH2:16][CH:15]2[N:17]([C:18]3[C:19]4[C:26]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)=[C:25]([C:33](=[O:38])[NH:34][CH:35]([CH3:37])[CH3:36])[S:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH:12]([CH2:13][CH2:14]2)[CH2:11]1)(=O)=O.[N-:39]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN1C(=O)CCC1.C(Cl)Cl>[NH2:39][CH2:6][CH2:7][O:8][CH2:9][CH:10]1[CH2:11][C@H:12]2[N:17]([C:18]3[C:19]4[C:26]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)=[C:25]([C:33]([NH:34][CH:35]([CH3:37])[CH3:36])=[O:38])[S:24][C:20]=4[N:21]=[CH:22][N:23]=3)[C@H:15]([CH2:14][CH2:13]2)[CH2:16]1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 89579738HCID 89579738, compound

Product 1

HCID 117739744HCID 117739744, compoundYield 41.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

2-[[8-[6-(isopropylcarbamoyl)-5-phenyl-thieno[2,3-d]pyrimidin-4-yl]-8-azabicyclo[3.2.1]octan-3-yl]methoxy]ethyl methanesulfonate (0.3 g, 0.5 mmol) was dissolved in NMP (2 mL). Sodium azide (0.2 g, 3 mmol) was added and the reaction heated to 150° C. in the microwave for 30 minutes. The reaction mixture was diluted with DCM (20 mL), washed with water (2×20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was dissolved in THF (5 mL). Triphenylphosphine (0.2 g, 0.8 mmol) was added and the reaction stirred overnight at room temperature. It was heated to reflux for 5 hours. The solvent was removed at reduced pressure. The resulting residue was taken up in DCM, washed with water, dried over Na2SO4 and concentrated at reduced pressure. The resulting residue was purified by flash chromatography, eluting with a gradient of DCM to 90/10/1 DCM/MeOH/NH4OH to afford 4-[(1R,5S)-3-(2-aminoethoxymethyl)-8-azabicyclo[3.2.1]octan-8-yl]-N-isopropyl-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxamide (100 mg).

Workup

  1. washwashed with water (2×20 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in THF (5 mL)
  5. temperatureIt was heated
  6. temperatureto reflux for 5 hours
  7. customThe solvent was removed at reduced pressure
  8. washwashed with water
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated at reduced pressure
  11. customThe resulting residue was purified by flash chromatography
  12. washeluting with a gradient of DCM to 90/10/1 DCM/MeOH/NH4OH

Sources & evidence

ORD record
ord-afc1fe702b2c435a9f46550cedf6c23e
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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