Hydrochloric Acid → HCID 178494459, compound

HRID 1751706Notes

Reaction equation

HRID 1751706 reaction equation
[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][N:7]([C:9](OC(C)(C)C)=[O:10])[CH:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32]([B:37]2[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]2)=[CH:31][CH:30]=3)[CH2:5]1.Cl.[CH3:47][O:48][C@H:49]([CH3:59])[C@H:50]([NH:54][C:55]([O:57][CH3:58])=[O:56])C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][N:7]([C:9](=[O:10])[CH:50]([NH:54][C:55](=[O:56])[O:57][CH3:58])[CH:49]([O:48][CH3:47])[CH3:59])[CH:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32]([B:37]2[O:38][C:39]([CH3:45])([CH3:44])[C:40]([CH3:42])([CH3:43])[O:41]2)=[CH:31][CH:30]=3)[CH2:5]1

Participants

8

Reactant 5

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 59540170(2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acidHCID 178494460HCID 178494460, compound

Product 1

HCID 178494459HCID 178494459, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
40 °C

Procedure

To a solution of tert-butyl 4-(methoxymethyl)-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidine-1-carboxylate (0.25 g, 0.41 mmol) in a mixture of CH2Cl2 (4.0 mL) and MeOH (1.0 mL) was added HCl (in dioxanes, 4M, 3.0 mL, 12.0 mmol). The resulting solution was stirred at 40° C. for 45 min. The solution was cooled to room temperature and concentrated to dryness under reduced pressure. To the crude intermediate in CH2Cl2 (4.0 mL) was added (2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid (0.08 g, 0.42 mmol), HATU (0.17 g, 0.45 mmol), and DIPEA (0.4 mL, 2.3 mmol). The resulting solution was stirred at room temperature for 48 h and diluted with CH2Cl2. The solution was washed with brine. The aqueous layer was back extracted with CH2Cl2 (2×). The resulting organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (30% to 100% EtOAc (w/5% MeOH)/Hexanes to 80% MeOH/EtOAc) to afford methyl (1-{4-(methoxymethyl)-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidin-1-yl}-3-methoxy-1-oxobutan-2-yl)carbamate (0.24 g, 92%).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated to dryness under reduced pressure
  3. stirringThe resulting solution was stirred at room temperature for 48 h
  4. washThe solution was washed with brine
  5. extractionThe aqueous layer was back extracted with CH2Cl2 (2×)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (30% to 100% EtOAc (w/5% MeOH)/Hexanes to 80% MeOH/EtOAc)

Sources & evidence

ORD record
ord-629eab4aea1f41c5a762a5a476f4a6bf
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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