Hydrochloric Acid → HCID 178502145, compound

HRID 2172420Notes

Reaction equation

HRID 2172420 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, 0.73 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-778f26b6bb704d96aae64af750be8c68
Source dataset
uspto-grants-2015_06
Patent number
US09051340B2

Reaction notes

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