1,4-Dibromobutane → {1-[1-(4-Pyrrolidin-1-ylmethyl-pyridin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid benzyl ester

HRID 1040510Notes

Reaction equation

Cl.Cl.[CH2:3]([O:10][C:11](=[O:30])[NH:12][C:13]1([C:16](=[O:29])[NH:17][C:18]2([C:21]3[CH:26]=[C:25]([CH2:27][NH2:28])[CH:24]=[CH:23][N:22]=3)[CH2:20][CH2:19]2)[CH2:15][CH2:14]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:32][CH2:33][CH2:34][CH2:35]Br.C([O-])([O-])=O.[Na+].[Na+]>CC(N(C)C)=O.CC#N.O>[CH2:3]([O:10][C:11](=[O:30])[NH:12][C:13]1([C:16](=[O:29])[NH:17][C:18]2([C:21]3[CH:26]=[C:25]([CH2:27][N:28]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH:24]=[CH:23][N:22]=3)[CH2:19][CH2:20]2)[CH2:14][CH2:15]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 80 °C

Procedure

{1-[1-(4-Aminomethyl-pyridin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid benzyl ester dihydrochloride (200 mg, 0.441 mmol) was dissolved in dry DMA (5 mL). 1,4-Dibromobutane (0.264 mL, 2.206 mmol) was added followed by Na2CO3 (0.234 g, 2.206 mmol). The reaction mixture was heated at 80° C. in a microwave reactor for 20 min. The reaction mixture was diluted with MeCN (4 mL) and water (1 mL) and filtered. The resultant crude product was purified by mass triggered LCMS using 5-35% MeCN/water as the gradient to afford 67 mg of {1-[1-(4-Pyrrolidin-1-ylmethyl-pyridin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid benzyl ester.

Workup

filtrationfiltered
customThe resultant crude product was purified by mass

Sources & evidence

ORD record: ord-ce4459e9b1b644639872b9020b4afb03
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552205B2

Reaction notes

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