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 79892Notes

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 2x 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 2x with EtOAc
dry with materialthe combined organics were dried over MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-0c3c8277163c4af98f01bc9325005dd9
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841278B2

Reaction notes

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