Potassium Carbonate → HCID 86708746, compound

HRID 1751456Notes

Reaction equation

HRID 1751456 reaction equation
C(O[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[NH:38][C:39]([CH:42]6[CH2:46][C:45]([F:48])([F:47])[CH2:44][N:43]6[C:49](=[O:62])[CH:50]([NH:57][C:58]([O:60][CH3:61])=[O:59])[CH:51]6[CH2:56][CH2:55][O:54][CH2:53][CH2:52]6)=[N:40][CH:41]=5)=[CH:33][CH:32]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[CH3:69][O:70][C:71]([NH:73][CH:74]([C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)C(O)=O)=[O:72].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>CCO.[Pd].C(Cl)Cl>[CH3:61][O:60][C:58](=[O:59])[NH:57][CH:50]([CH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1)[C:49]([N:43]1[CH2:44][C:45]([F:47])([F:48])[CH2:46][CH:42]1[C:39]1[NH:38][C:37]([C:34]2[CH:35]=[CH:36][C:31]([C:26]3[CH:25]=[CH:24][C:23]4[C:28](=[CH:29][CH:30]=[C:21]([C:18]5[NH:17][C:16]([CH:12]6[CH2:13][CH2:14][CH2:15][N:11]6[C:9](=[O:10])[CH:74]([NH:73][C:71]([O:70][CH3:69])=[O:72])[C:78]6[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=6)=[N:20][CH:19]=5)[CH:22]=4)[CH:27]=3)=[CH:32][CH:33]=2)=[CH:41][N:40]=1)=[O:62]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 596264N-Methoxycarbonyl-2-phenylglycineHCID 696753852-(5-{6-[4-(2-{4,4-Difluoro-1-[2-methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid benzyl esterHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 86708746HCID 86708746, compoundYield 111%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-{6-[4-(2-{4,4-Difluoro-1-[2-methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid benzyl ester (0.13 g, 0.15 mmol) in EtOH (3.5 mL) was added Palladium on carbon (10%, 0.08 g, 0.08 mmol) and Potassium Carbonate (0.07 g, 0.48 mmol). The slurry was stirred at room temperature under an atmosphere of H2 for 3 h. The slurry was filtered through celite and washed with EtOH. The filtrate was concentrated to an oil and diluted with CH2Cl2 (3 mL) and filtered an additional time. Methoxycarbonylamino-phenyl-acetic acid (0.05 g, 0.03 mmol) and Potassium Phosphate (0.04 g, 0.16 mmol) were added and the resulting slurry was cooled to 0° C. (external, ice). COMU (0.09 g, 0.02 mmol) was added and the reaction was stirred at 0° C. for 2 h. The slurry was diluted with CH2Cl2 and filtered through celite. The filtrate was concentrated and purified by preparative HPLC (Gemini, 15→50% MeCN in H2O (0.1% TFA)) to provide to provide [2-(4,4-Difluoro-2-{5-[4-(6-{2-[1-(2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid methyl ester (0.03 g, 17%). LCMS-ESI+: calc'd for C49H50F2N8O7: 900.38 (M+); Found: 901.4 (M+H+).

Workup

  1. filtrationThe slurry was filtered through celite
  2. washwashed with EtOH
  3. concentrationThe filtrate was concentrated to an oil
  4. additiondiluted with CH2Cl2 (3 mL)
  5. filtrationfiltered an additional time
  6. temperaturethe resulting slurry was cooled to 0° C. (external, ice)
  7. stirringthe reaction was stirred at 0° C. for 2 h
  8. filtrationfiltered through celite
  9. concentrationThe filtrate was concentrated
  10. custompurified by preparative HPLC (Gemini, 15→50% MeCN in H2O (0.1% TFA))
  11. customto provide

Sources & evidence

ORD record
ord-b357133f7b1e4f1796aeba0e23388d34
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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