Hydrochloric Acid → HCID 178455978, compound

HRID 1431822Notes

Reaction equation

HRID 1431822 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-960806db37fa452299b04742460be300
Source dataset
uspto-grants-2015_01
Patent number
US08940718B2

Reaction notes

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