1,2,3,4-Tetrahydroisoquinoline → HCID 68858904, compound

HRID 1726430Notes

Reaction equation

HRID 1726430 reaction equation
[CH2:1]([O:3][C:4]([C@@:6]12[CH2:24][C@H:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:14](=[O:33])[N:13]1[C@@H:9]([CH2:10][C@@H:11]([OH:34])[CH2:12]1)[C:8](=[O:35])[NH:7]2)=[O:5])[CH3:2].C1N=CN([C:41]([N:43]2[CH:47]=N[CH:45]=[CH:44]2)=[O:42])C=1.C(Cl)Cl.CO.C1[C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)CCN1>C(Cl)Cl>[CH2:1]([O:3][C:4]([C@@:6]12[CH2:24][C@H:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]([NH:25][C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[C:14](=[O:33])[N:13]1[C@@H:9]([CH2:10][C@@H:11]([O:34][C:41]([N:43]3[CH2:44][CH2:45][C:62]4[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=4)[CH2:47]3)=[O:42])[CH2:12]1)[C:8](=[O:35])[NH:7]2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 682631,1'-CarbonyldiimidazoleHCID 21226129Dichloromethane methanolHCID 68789818HCID 68789818, compound

Product 1

HCID 68858904HCID 68858904, compoundYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The macrocyclic intermediate 10 (110 mg, 0.22 mmol) was dissolved in DCM (2.2 mL), followed by addition of CDI (45 mg, 0.27 mmol) in one portion. The reaction was stirred at rt overnight. After 15 h, the reaction was complete as monitored by TLC (DCM/MeOH 9:1). 1,2,3,4-tetrahydroisoquinoline (0.14 mL, 1.1 mmol) was added to the reaction drop-wise, and the reaction was stirred at rt for overnight. After 22 h, TLC showed reaction complete. The reaction was diluted with DCM (6 mL) and washed with 1N aq. HCl (2×2 mL), sat. sodium bicarbonate (2 mL), brine (2 mL), dried (Na2SO4), and concentrated down. The crude was purified on silica gel (Biotage 40S, eluent: 2 to 4% MeOH in DCM), giving 11 as a pale yellowish foamy powder (131 mg, 90%).

Workup

  1. waitAfter 15 h
  2. stirringthe reaction was stirred at rt for overnight
  3. waitAfter 22 h
  4. customreaction complete
  5. washwashed with 1N aq. HCl (2×2 mL), sat. sodium bicarbonate (2 mL), brine (2 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated down
  8. customThe crude was purified on silica gel (Biotage 40S, eluent: 2 to 4% MeOH in DCM)

Sources & evidence

ORD record
ord-fec98e2856214830b6de942e2e320834
Source dataset
uspto-grants-2009_02
Patent number
US07491794B2

Reaction notes

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