Acetic Acid → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-((1-(tetrahydro-2H-pyran-4-yl)ethyl)amino)benzamide

HRID 2202060Notes

Reaction equation

HRID 2202060 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[C:5]([NH:7][CH2:8][CH:9]([OH:21])[CH2:10][N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12]1)=[O:6].[O:25]1[CH2:30][CH2:29][CH:28]([C:31](=O)[CH3:32])[CH2:27][CH2:26]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:19][CH2:20][N:11]1[CH2:10][CH:9]([OH:21])[CH2:8][NH:7][C:5](=[O:6])[C:4]1[CH:22]=[CH:23][CH:24]=[C:2]([NH:1][CH:31]([CH:28]2[CH2:29][CH2:30][O:25][CH2:26][CH2:27]2)[CH3:32])[CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 98773651-(Tetrahydro-2H-pyran-4-yl)ethanoneHCID 902415853-amino-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)benzamide

Product 1

HCID 76901175N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-((1-(tetrahydro-2H-pyran-4-yl)ethyl)amino)benzamideYield 8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
22 °C

Procedure

A solution of 3-amino-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)benzamide (130 mg, 0.4 mmol), 1-(tetrahydro-2H-pyran-4-yl)ethanone (52 mg, 0.4 mmol) and AcOH (0.1 mL) in MeOH (10 mL). The mixture was stirred at 22° C. for 1 h, then NaBH3CN (76 mg, 1.2 mmol) was added. The mixture was stirred at 22° C. for 4 h. The reaction mixture was concentrated and quenched with water. The mixture solution was extracted with DCM, the combined organic layers were concentrated and the residue was purified by prep-TLC to give the desired compound (14.0 mg, Yield 8%). 1H NMR (CD3OD, 400 MHz): δ 6.90-7.07 (m, 6H), 6.81 (d, J=7.5 Hz, 1H), 6.64 (d, J=8.03 Hz, 1H), 3.98-4.04 (m, 1H), 3.87 (d, J=11.3 Hz, 2H), 3.70 (s, 2H), 3.28-3.45 (m, 5H), 2.82 (brs, 4H), 2.56-2.65 (m, 2H), 1.70 (d, J=13.8 Hz, 1H), 1.57 (brs, 1H), 1.17-1.37 (m, 3H), 1.04 (d, J=6.3 Hz, 3H). LCMS (m/z): 438.3 (M+1).

Workup

  1. stirringThe mixture was stirred at 22° C. for 4 h
  2. concentrationThe reaction mixture was concentrated
  3. customquenched with water
  4. extractionThe mixture solution was extracted with DCM
  5. concentrationthe combined organic layers were concentrated
  6. customthe residue was purified by prep-TLC

Sources & evidence

ORD record
ord-9d805e6876e141a0ab998478c7a98b1f
Source dataset
uspto-grants-2016_06
Patent number
US09365519B2

Reaction notes

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