Hydrochloric Acid → HCID 178455978, compound

HRID 1509688Notes

Reaction equation

HRID 1509688 reaction equation
C(O[C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]1[NH:20][C:19]2[C:21]3[C:26]([CH:27]=[CH:28][C:18]=2[N:17]=1)=[CH:25][C:24]1[C:29]2[C:34]([CH2:35][O:36][C:23]=1[CH:22]=3)=[CH:33][C:32]([C:37]1[NH:41][C:40]([C@@H:42]3[CH2:46][CH2:45][C@H:44]([CH3:47])[N:43]3C(OC(C)(C)C)=O)=[N:39][CH:38]=1)=[CH:31][CH:30]=2)=[O:7])(C)(C)C.Cl.[CH3:56][O:57][C:58]([NH:60][C@@H:61]([C@@H:65]([CH3:68])[CH2:66][CH3:67])[C:62]([OH:64])=O)=[O:59].CN(C(ON1N=N[C:79]2[CH:80]=[CH:81][CH:82]=[N:83]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:93]CN(C(C)C)C(C)C.CO.C[CH2:105][O:106][C:107](C)=[O:108]>C(Cl)Cl.CN(C=O)C.CO>[CH3:105][O:106][C:107]([NH:83][C@@H:82]([C@@H:81]([CH3:93])[CH2:80][CH3:79])[C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]1[NH:20][C:19]2[C:21]3[C:26]([CH:27]=[CH:28][C:18]=2[N:17]=1)=[CH:25][C:24]1[C:29]2[C:34]([CH2:35][O:36][C:23]=1[CH:22]=3)=[CH:33][C:32]([C:37]1[NH:41][C:40]([C@@H:42]3[CH2:46][CH2:45][C@H:44]([CH3:47])[N:43]3[C:62](=[O:64])[C@@H:61]([NH:60][C:58](=[O:59])[O:57][CH3:56])[C@@H:65]([CH3:68])[CH2:66][CH3:67])=[N:39][CH:38]=1)=[CH:31][CH:30]=2)=[O:7])=[O:108]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21584119Ethylacetate methanolHCID 28378062L-Isoleucine, N-(methoxycarbonyl)-HCID 178495654HCID 178495654, compound

Product 1

HCID 178455978HCID 178455978, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (2S,5S)-2-(5-{2-[(2S,4S)-1-(tert-butoxycarbonyl)-4-(methoxymethyl)pyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (207 mg, 0.28 mmol) was dissolved in DCM (4 mL), MeOH (1 mL) and HCl (4 M in dioxane, 1 mL) was added. The reaction mixture was stirred for 1.5 h and then concentrated under reduced pressure. The crude residue was treated with (2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoic acid (106 mg, 0.56 mmol), HATU (214 mg, 0.56 mmol) and DMF (5 mL), then DIPEA (0.49 mL, 2.8 mmol) was added dropwise. After 30 min, the mixture was diluted with 10% MeOH/EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by HPLC to afford methyl {(2S,3S)-1-[(2S,5S)-2-(5-{2-[(2S,4S)-1-{(2S,3S)-2-[(methoxycarbonyl)amino]-3-methylpentanoyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl}carbamate (132 mg, 69%). LCMS-ESI+: calculated for C45H54N8O7: 876.45; observed [M+1]+: 879.02

Workup

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 30 min
  3. washwashed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by HPLC

Sources & evidence

ORD record
ord-726da6e2587f416f805741214b43132a
Source dataset
uspto-grants-2015_12
Patent number
US09221833B2

Reaction notes

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