3-Phenylcyclobutan-1-amine → Ethyl 6-chloro-7-(4-(3-phenylcyclobutylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1021531Notes

Reaction equation

HRID 1021531 reaction equation
[C:1]1([CH:7]2[CH2:10][CH:9]([NH2:11])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1)[O:19][CH2:18][CH2:17][CH:16]2[C:33]([O:35][CH2:36][CH3:37])=[O:34].Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CN(C)C1C=CN=CC=1.CCOC(C)=O>[Cl:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](=[O:29])[NH:11][CH:9]3[CH2:8][CH:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:10]3)=[CH:26][CH:25]=1)[O:19][CH2:18][CH2:17][CH:16]2[C:33]([O:35][CH2:36][CH3:37])=[O:34]

Participants

7

Reactant 3

HCID 5229613-Phenylcyclobutan-1-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 67080785Ethyl 6-chloro-7-(4-(3-phenylcyclobutylcarbamoyl)phenoxy)chroman-4-carboxylateYield 49.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-phenylcyclobutanamine (0.101 g, 0.686 mmol) in DMF (2 ml) was added 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.129 g, 0.343 mmol), N,N-dimethylpyridin-4-amine (0.00838 g, 0.0686 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.0789 g, 0.412 mmol), and the reaction was stirred for 16 hours at ambient temperature. The reaction was diluted with EtOAc and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was on a Biotage SP1 system eluting with a 5-70% EtOAc in hexanes linear gradient to yield 86 mg of the title compound (49.5% yield).

Workup

  1. washwashed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washeluting with a 5-70% EtOAc in hexanes linear gradient

Sources & evidence

ORD record
ord-76ce6e629aaa4a9c9a5047cda442b7dd
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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