o-Bis(bromomethyl)benzene → (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(isoindolin-2-yl)pyrrolidine-2-carboxamide

HRID 1630285Notes

Reaction equation

HRID 1630285 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9]Br.[N:11]1([CH2:16][C:17]([N:19]2[CH2:23][C@H:22]([NH2:24])[CH2:21][C@H:20]2[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)=[O:26])=[O:18])[CH:15]=[N:14][CH:13]=[N:12]1>>[N:11]1([CH2:16][C:17]([N:19]2[CH2:23][C@H:22]([N:24]3[CH2:9][C:4]4[C:3](=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH2:2]3)[CH2:21][C@H:20]2[C:25]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][C:35]3[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=3)=[CH:32][CH:33]=2)=[O:26])=[O:18])[CH:15]=[N:14][CH:13]=[N:12]1

Participants

3

Reactant 2

HCID 66665o-Bis(bromomethyl)benzeneHCID 67010477HCID 67010477, compound

Product 1

HCID 45376627(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(isoindolin-2-yl)pyrrolidine-2-carboxamideYield 11%

Procedure

Proceeding as in Example 7, but substituting 1,2-bis(bromomethyl)benzene and (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide gave Compound 260, (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(isoindolin-2-yl)pyrrolidine-2-carboxamide (47 mg, 0.088 mmol, 11%). 1H-NMR (400 MHz, DMSO-d6): 10.10 (s, 1H), 8.45 (s, 1H), 7.96 (s, 1H), 7.60 (d, J=10.0 Hz, 2H), 7.29-7.17 (m, 6H), 7.03-6.95 (m, 4H), 5.34-5.30 (m, 2H), 4.56-4.52 (m, 1H), 3.95 (s, 4H), 3.71-3.60 (m, 1H), 3.52-3.46 (m, 2H), 2.31-2.24 (m, 1H), 2.17-2.09 (m, 1H). MS (EI) for C29H27FN6O3. found 527.2 (MH+).

Sources & evidence

ORD record
ord-e6a53b7cd4964cd39af6cc9dc3f0d5fb
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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