1,1'-Carbonyldiimidazole → HCID 68787238, compound

HRID 1726438Notes

Reaction equation

HRID 1726438 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 product from Step C (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). Isoindoline (0.12 mL, 1.1 mmol) was added to the reaction drop-wise, and the reaction was stirred at 40° C. for overnight. After 22 h, TLC showed reaction complete. The reaction was cooled to rt, 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 the desired product as a white powder (131 mg, 90%).

Workup

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

Sources & evidence

ORD record
ord-bc3770f79d90448382f566ecc95b270d
Source dataset
uspto-grants-2009_02
Patent number
US07491794B2

Reaction notes

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