6-(2-Amino-4-bromo-phenylcarbamoyl)-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester → 6-(6-Bromo-1H-benzoimidazol-2-yl)-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester

HRID 417640Notes

Reaction equation

[CH2:1]([O:8][C:9]([N:11]1[CH:17]([C:18](=O)[NH:19][C:20]2[CH:25]=[C:24]([Br:26])[CH:23]=[CH:22][C:21]=2[NH2:27])[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(N1C(C(=O)NC2C=CC(Br)=CC=2N)CC2(CC2)C1)=O)C1C=CC=CC=1>CC(O)=O>[CH2:1]([O:8][C:9]([N:11]1[CH:17]([C:18]2[NH:19][C:20]3[CH:25]=[C:24]([Br:26])[CH:23]=[CH:22][C:21]=3[N:27]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 6-(2-Amino-5-bromo-phenylcarbamoyl)-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester and 6-(2-Amino-4-bromo-phenylcarbamoyl)-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester (1.446 g, 3.25 mmol) was dissolved in AcOH (20 mL) and the reaction mixture was stirred at 40° C. for 18 hours then concentrated under reduced pressure. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3. The aqueous layer was extracted 2× with EtOAc and the combined organics were dried over MgSO4, filtered and concentrated to provide 6-(6-Bromo-1H-benzoimidazol-2-yl)-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester (1.385 g, 100%).

Workup

concentrationthen concentrated under reduced pressure
dissolutionThe residue was dissolved in EtOAc
washwashed with saturated aqueous NaHCO3
extractionThe aqueous layer was extracted 2× with EtOAc
dry with materialthe combined organics were dried over MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-b89c9f01a96f4abaafe4a9c56963d225
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088368B2

Reaction notes

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