N,N-Diethyl-1,3-propanediamine → (1aRS,7bSR)-5-[2-(3-diethylaminopropylamino)benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927872Notes

Reaction equation

[CH2:1]([N:3]([CH2:8][CH3:9])[CH2:4][CH2:5][CH2:6][NH2:7])[CH3:2].F[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH:20][C:21]1[C:30]([C:31]([OH:33])=[O:32])=[C:29]2[C:24]([CH:25]3[CH2:34][CH:26]3[CH2:27][O:28]2)=[CH:23][CH:22]=1)(=[O:19])=[O:18]>CN1C(=O)CCC1.O>[CH2:1]([N:3]([CH2:8][CH3:9])[CH2:4][CH2:5][CH2:6][NH:7][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH:20][C:21]1[C:30]([C:31]([OH:33])=[O:32])=[C:29]2[C:24]([CH:25]3[CH2:34][CH:26]3[CH2:27][O:28]2)=[CH:23][CH:22]=1)(=[O:19])=[O:18])[CH3:2]

Participants

Conditions

Temperature: 140 °C

Procedure

3-Diethylaminopropyl amine (0.975 g) was added to a solution of (1aRS,7bSR)-5-(2-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (Intermediate 67, 0.091 g) in NMP (3 mL) and the mixture was heated at 140° C. in a sealed tube for 36 hours. After cooling, the mixture was diluted with water (2 mL) and the solution was purified by preparative HPLC (C18) eluting with a mixture of methanol and water, containing 0.1% formic acid, with a gradient of 10-98% to give (1aRS,7bSR)-5-[2-(3-diethylaminopropylamino)benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.039 g) as a white solid.

Workup

temperatureAfter cooling
customthe solution was purified by preparative HPLC (C18)
washeluting with a mixture of methanol and water
additioncontaining 0.1% formic acid

Sources & evidence

ORD record: ord-406df542c49c4a11aaa13b2e4cbd760f
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290472B2

Reaction notes

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