Water → (1-{2-[5-(7-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9-oxo-9H-fluoren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 2392383Notes

Reaction equation

HRID 2392383 reaction equation
[CH3:1][O:2][C:3](=[O:63])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:33]=[CH:32][C:31]3[C:30]4[C:25](=[CH:26][C:27]([C:34]5[CH:60]=[CH:59][C:37]6[N:38]=[C:39]([CH:41]7[CH:46]8[CH2:47][CH:43]([CH2:44][CH2:45]8)[N:42]7[C:48](=[O:58])[CH:49]([NH:53][C:54]([O:56][CH3:57])=[O:55])[CH:50]([CH3:52])[CH3:51])[NH:40][C:36]=6[CH:35]=5)=[CH:28][CH:29]=4)[C:24](F)(F)[C:23]=3[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[OH2:64]>CC#N.C(O)(C(F)(F)F)=O>[CH3:1][O:2][C:3](=[O:63])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:33]=[CH:32][C:31]3[C:30]4[C:25](=[CH:26][C:27]([C:34]5[CH:60]=[CH:59][C:37]6[N:38]=[C:39]([CH:41]7[CH:46]8[CH2:47][CH:43]([CH2:44][CH2:45]8)[N:42]7[C:48](=[O:58])[CH:49]([NH:53][C:54]([O:56][CH3:57])=[O:55])[CH:50]([CH3:52])[CH3:51])[NH:40][C:36]=6[CH:35]=5)=[CH:28][CH:29]=4)[C:24](=[O:64])[C:23]=3[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

5

Reactant 2

HCID 962WaterHCID 66620162(1-{2-[5-(9,9-Difluoro-7-{2-[2-(2-methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl]-9H-fluoren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 66620781(1-{2-[5-(7-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9-oxo-9H-fluoren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6342AcetonitrileSolvent

Procedure

(1-{2-[5-(9,9-Difluoro-7-{2-[2-(2-methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9H-fluoren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (10 mg) is dissolve in MeCN (1 mL) and water (1 mL). 1 drop of TFA was added. The mixture was treated with long wavelengh UV light at room temprature for 2 hours. The reaction crude was concentrated down and purified by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA). Product was lyophilized to give (1-{2-[5-(7-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9-oxo-9H-fluoren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Example DL) (3.7 mg).

Workup

  1. additionThe mixture was treated with long wavelengh UV light at room temprature for 2 hours
  2. customThe reaction crude
  3. concentrationwas concentrated down
  4. custompurified by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-c3d55872fd0f49908943608eff458f0f
Source dataset
uspto-grants-2012_09
Patent number
US08273341B2

Reaction notes

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