1,1'-Carbonyldiimidazole → HCID 68787238, compound

HRID 2069168Notes

Reaction equation

HRID 2069168 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:61]2[C:56](=[CH:57][CH:58]=C[CH:60]=2)CN1>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][C:45]4[C:58](=[CH:57][CH:56]=[CH:61][CH:60]=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 682631,1'-CarbonyldiimidazoleHCID 422478IsoindolineHCID 21226129Dichloromethane methanolHCID 68789818HCID 68789818, compound

Product 1

HCID 68787238HCID 68787238, compoundYield 93.2%

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). 2,3-Dihydro-1H-isoindole (0.14 mL, 1.1 mmol) was added to the reaction drop-wise, and the reaction was stirred at rt 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 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-9b8a0e0c394445269951f8d65c76fdb6
Source dataset
uspto-grants-2012_10
Patent number
US08299021B2

Reaction notes

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