P,P-Diphenylphosphinic azide → HCID 178461227, compound

HRID 81253Notes

Reaction equation

HRID 81253 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:16][C:12]=3[CH:11]=[C:10](C(O)=O)[N:9]=2)[CH:5]=[N:6][CH:7]=1.C1(P([N:54]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C=O)C.O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[N:16][C:12]=3[CH:11]=[C:10]([NH2:54])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 199401P,P-Diphenylphosphinic azideHCID 178461226HCID 178461226, compound

Product 1

HCID 178461227HCID 178461227, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (Example 3.22, prepared from Example 2.1, Step 4 using a procedure similar to that described for Example 1.1, Step 5; 500 mg, 0.91 mmol) in DMF (6 mL) was added TEA (0.2 mL, 1.83 mmol), and the reaction was deoxygenated by purging with nitrogen for 5 minutes. To this reaction mixture was added diphenyl phosphoryl azide (0.4 mL, 1.83 mmol) and the reaction flask was sealed. The mixture was stirred at rt for 1 h and then H2O (2 mL) was added. Again, the reaction flask was sealed and the reaction was heated at 90° C. for 1.5 h. The reaction was then diluted with water and EtOAc. The organic layer was separated and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (2% MeOH/CH2Cl2) to yield 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridin-6-amine. MS ES/APCl calc'd. for C29H33ClN6O [M+H]+ 517. found 517.

Workup

  1. customthe reaction was deoxygenated
  2. customby purging with nitrogen for 5 minutes
  3. customthe reaction flask was sealed
  4. customAgain, the reaction flask was sealed
  5. temperaturethe reaction was heated at 90° C. for 1.5 h
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialThe organic layer was dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography (2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-55043cd261444b3694b5042badf7b6c9
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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