Hydrochloric Acid → HCID 178502499, compound

HRID 2038846Notes

Reaction equation

HRID 2038846 reaction equation
C(O[C:6]([N:8]1[C@@H:12]([CH3:13])[CH2:11][CH2:10][C@H:9]1[C:14]1[NH:18][C:17]2[C:19]3[C:24]([CH:25]=[CH:26][C:16]=2[N:15]=1)=[CH:23][C:22]1[C:27]2[C:32]([CH2:33][O:34][C:21]=1[CH:20]=3)=[CH:31][C:30]([C:35]1[NH:39][C:38]([C@@H:40]3[CH2:44][CH2:43][C@H:42]([CH3:45])[N:41]3[C:46](OC(C)(C)C)=[O:47])=[N:37][CH:36]=1)=[CH:29][CH:28]=2)=[O:7])(C)(C)C.Cl.[CH3:54][O:55][C:56]([NH:58][C@@H:59]([CH:63]([CH3:65])[CH3:64])C(O)=O)=[O:57].CN(C(ON1N=NC2[CH:77]=[CH:78][CH:79]=[N:80]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:90]CN(C(C)C)C(C)C.CO.C[CH2:102][O:103][C:104](C)=[O:105]>C(Cl)Cl.CN(C=O)C.CO>[CH3:102][O:103][C:104]([NH:80][C@@H:79]([CH:78]([CH3:90])[CH3:77])[C:6]([N:8]1[C@@H:12]([CH3:13])[CH2:11][CH2:10][C@H:9]1[C:14]1[NH:18][C:17]2[C:19]3[C:24]([CH:25]=[CH:26][C:16]=2[N:15]=1)=[CH:23][C:22]1[C:27]2[C:32]([CH2:33][O:34][C:21]=1[CH:20]=3)=[CH:31][C:30]([C:35]1[NH:39][C:38]([C@@H:40]3[CH2:44][CH2:43][C@H:42]([CH3:45])[N:41]3[C:46](=[O:47])[C@@H:59]([NH:58][C:56](=[O:57])[O:55][CH3:54])[CH:63]([CH3:64])[CH3:65])=[N:37][CH:36]=1)=[CH:29][CH:28]=2)=[O:7])=[O:105]

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 21584119Ethylacetate methanolHCID 178461193HCID 178461193, compound

Product 1

HCID 178502499HCID 178502499, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (2S,5S)-2-(5-{2-[(2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (164 mg, 0.23 mmol) was dissolved in DCM (7 mL), MeOH (1.5 mL) and HCl (4 M in dioxane, 1.5 mL) was added. The reaction mixture was stirred for 16 h and then concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (81 mg, 0.46 mmol), HATU (175 mg, 0.46 mmol) and DMF (5 mL), then DIPEA (0.4 mL, 2.34 mmol) was added dropwise. After 35 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)-1-[(2S,5S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-methylpyrrolidin-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-oxobutan-2-yl}carbamate (132 mg, 69%). LCMS-ESI+: calculated for C45H54N8O7: 818.41; observed [M+1]+: 820.19. 1H NMR (CD3OD): 8.492 (m, 1H), 8.179-7.538 (m, 7H), 5.267-5.201 (m, 3H), 5.125-5.082 (m, 1H), 4.070 (m, 1H), 3.383-3.592 (m, 4H), 3.225 (s, 3H), 2.466-2.249 (m, 5H), 1.992-1.892 (m, 3H), 1.568 (d, 3H, J=6.4 Hz), 1.490 (d, 3H, J=6.8 Hz), 1.266 (m, 2H), 1.020-0.806 (m, 14H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 35 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-28073283ce444c7d9f23d7efd2b56d01
Source dataset
uspto-grants-2013_11
Patent number
US08575135B2

Reaction notes

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