Hydrochloric Acid → HCID 178502145, compound

HRID 1751601Notes

Reaction equation

HRID 1751601 reaction equation
C[O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[CH2:16][CH2:15][CH2:14][CH:13]1[C:17]1[NH:18][C:19]([C:22]2[CH:27]=[C:26]3[CH2:28][O:29][C:30]4[CH:54]=[C:53]5[C:33]([CH:34]=[CH:35][C:36]6[N:40]=[C:39]([CH:41]7[CH2:45][CH2:44][CH2:43][N:42]7[C:46](OC(C)(C)C)=[O:47])[NH:38][C:37]=65)=[CH:32][C:31]=4[C:25]3=[CH:24][CH:23]=2)=[CH:20][N:21]=1)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].Cl.[CH3:56][O:57][C:58]([NH:60][C@H:61]([C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)C(O)=O)=[O:59].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C.C(O)C>[CH3:56][O:57][C:58]([NH:60][CH:61]([C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)[C:46]([N:42]1[CH2:43][CH2:44][CH2:45][CH:41]1[C:39]1[NH:38][C:37]2[C:53]3[C:33]([CH:34]=[CH:35][C:36]=2[N:40]=1)=[CH:32][C:31]1[C:25]2[C:26]([CH2:28][O:29][C:30]=1[CH:54]=3)=[CH:27][C:22]([C:19]1[NH:18][C:17]([CH:13]3[CH2:14][CH2:15][CH2:16][N:12]3[C:10](=[O:11])[CH:6]([NH:5][C:3](=[O:4])[OH:2])[CH:7]([CH3:8])[CH3:9])=[N:21][CH:20]=1)=[CH:23][CH:24]=2)=[O:47])=[O:59]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178502301HCID 178502301, compound

Product 1

HCID 178502145HCID 178502145, compoundYield 45.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 2-[9-(2-{1-[N-(methoxycarbonyl)valyl]pyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidine-1-carboxylate (462 mg, 0.63 mmol), ethanol (6 mL) and concentrated HCl (2 mL) was heated to 60° C. for 1 hour. The reaction was concentrated and the crude material dissolved in DCM (6 mL). This solution was concentrated and to this material was added a solution of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (172 mg, 0.82 mmol) and COMU (311 mg, 073 mmol) in DMF (6 mL). To the resulting solution was added diisopropylethylamine (330 μL, 1.89 mmol). After stirring for 18 hours at room temperature, the reaction was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 45% ACN/H2O+0.1% TFA). The product fractions were lyophilized to give [1-(2-{5-[2-(1-{[(methoxycarbonyl)amino](phenyl)acetyl}pyrrolidin-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl]-1H-imidazol-2-yl}pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamic acid (231 mg, 45%). LCMS-ESI+: calculated for C46H48N8O78: 824.92; observed [M+1]+: 826.00.

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DCM (6 mL)
  3. concentrationThis solution was concentrated and to this material
  4. washwashed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. custompurified by preparative reverse phase HPLC (Gemini, 15 to 45% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-7018df7951b74127afd123a95d9e9fc4
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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