Tetrahydrofuran → HCID 89533754, compound

HRID 920219Notes

Reaction equation

HRID 920219 reaction equation
C1C2C(=CC=CC=2[C:11]([OH:13])=[O:12])C=CN=1.[CH2:14](N(CC)CC)C.Cl.[CH3:22][NH:23][O:24][CH3:25].O[N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2N=N1.Cl.C(N=C=N[CH2:42][CH2:43][CH2:44]N(C)C)C.[CH2:48]1[CH2:52][O:51][CH2:50][CH2:49]1>>[CH3:25][O:24][N:23]([CH3:22])[C:52]([C:48]1[CH:30]=[CH:35][CH:34]=[C:33]2[C:49]=1[CH2:50][N:27]([C:11]([O:13][C:43]([CH3:44])([CH3:14])[CH3:42])=[O:12])[CH2:31][CH2:32]2)=[O:51]

Participants

7

Reactant 6

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21393830Isoquinoline-8-carboxylic acid

Product 1

HCID 89533754HCID 89533754, compound

Procedure

With reference to Scheme 5, 12.5 g of 5-1 (45.1 mmol, prepared from commercially available isoquinoline-8-carboxylic acid by literature methods) and 18.85 g triethylamine (135 mmol) were dissolved in 150 mL THF. This solution was treated with N,O-dimethylhydroxylamine hydrochloride (5.72 g, 58.6 mmol), followed by 1.726 g N-hydroxybenzotriazole (HOBT, 11.27 mmol) and 8.73 g ethyl-(N′,N′-dimethylamino)propyl-carbodimide-hydrochloride (EDC, 45.5 mmol). The reaction was stirred overnight at RT. After removal of most of the solvent under reduced pressure, the residue was suspended in EtOAc (250 mL) and washed with 1N HCl (2×50 mL). The organic layer was washed with saturated sodium bicarbonate (2×50 mL), followed by brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by normal phase chromatography (0-50% EtOAc in hexane) yielded 5-2 (tert-butyl 8-[methoxy(methyl)-carbamoyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate) as a clear light yellow oil

Workup

  1. customAfter removal of most of the solvent under reduced pressure
  2. washwashed with 1N HCl (2×50 mL)
  3. washThe organic layer was washed with saturated sodium bicarbonate (2×50 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by normal phase chromatography (0-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-9df94060b47142a0937b84c59e86bb86
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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