HCID 59490386, compound → HCID 59490386, compound

HRID 2383491Notes

Reaction equation

HRID 2383491 reaction equation
COC1C=CC(CN2C3N=CC4CC(NC(=O)OC(C)(C)C)CCC=4C=3C=N2)=CC=1.[C:31]([NH:35][CH:36]1[CH2:45][C:44]2[CH:43]=[N:42][C:41]3[N:46]([CH2:49][C:50]4[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=4)[N:47]=[CH:48][C:40]=3[C:39]=2[CH2:38][CH2:37]1)([CH3:34])([CH3:33])[CH3:32].COC1C=CC(CN2C3N=CC4CC(N)CCC=4C=3C=N2)=CC=1>FC(F)(F)C(O)=O>[C:31]([NH:35][CH:36]1[CH2:45][C:44]2[CH:43]=[N:42][C:41]3[NH:46][N:47]=[CH:48][C:40]=3[C:39]=2[CH2:38][CH2:37]1)([CH3:34])([CH3:32])[CH3:33].[C:31]([NH:35][CH:36]1[CH2:45][C:44]2[CH:43]=[N:42][C:41]3[N:46]([CH2:49][C:50]4[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=4)[N:47]=[CH:48][C:40]=3[C:39]=2[CH2:38][CH2:37]1)([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 59490386HCID 59490386, compoundHCID 59490392HCID 59490392, compoundHCID 59490725HCID 59490725, compound

Product 2

HCID 46836547HCID 46836547, compoundHCID 59490386HCID 59490386, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-ylcarbamate (0.200 g, 0.49 mmol) in trifluoroacetic acid (2 mL) was heated at 65° C. for 16 hours. LC-Mass analysis of the reaction indicated the formation of both N-tert-butyl-3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-amine (LCMS [M+H]: 245, 45%, UV) and 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-ylamine (LCMS [M+H]: 189, 42%, UV). The reaction mixture was concentrated and then partitioned between dichloromethane (50 mL) and aqueous NaHCO3 (50 mL). The organic layer was separated, washed with brine (30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified using flash column chromatography (SiO2, 90% dichloromethane/10% methanol/3% ammonia) to give the pure desired product, N-tert-butyl-[3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-yl]-amine as a pale yellow solid (0.015 g, 12%). M.p.=>58° C.; 400 MHz 1H NMR (DMSO-d6) δ: 8.31 (s, 1H), 7.76 (s, 1H), 3.4-3.2 (br s, 1H), 3.15-2.94 (m, 3H), 2.93-2.82 (m, 1H), 2.6-2.52 (m, 1H), 2.05-1.8 (m, 2H), 1.65 (s, 9H); LCMS [M+H]: 245.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between dichloromethane (50 mL) and aqueous NaHCO3 (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (30 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-ab1deb80a2134cf5981b74fecfedfa05
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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