1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 5'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid amide

HRID 1691938ノート

反応式

HRID 1691938 の反応式
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:19][C:20]1[CH:21]=[CH:22][C:23]([N:26]2[CH2:31][CH2:30][CH:29]([C:32]([NH2:34])=[O:33])[CH2:28][CH2:27]2)=[N:24][CH:25]=1.[N+](C1C=CC(N2CCC(C(N)=O)CC2)=NC=1)([O-])=O.CCO.C1COCC1.CCOC(C)=O.Cl.C(N=C=NCCCN(C)C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C.[Pd]>[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([NH:19][C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH2:31][CH2:30][CH:29]([C:32]([NH2:34])=[O:33])[CH2:28][CH2:27]4)=[N:24][CH:25]=3)=[O:14])[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

参加物

10

反応物 5

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 31651361-(5-Nitropyridin-2-yl)piperidine-4-carboxamideHCID 167856881-(5-Aminopyridin-2-YL)piperidine-4-carboxamideHCID 18365940Tetrahydrofuran ethyl acetate ethanol

生成物 1

HCID 251197195'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid amide収率 26%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (3.42 g, 12.6 mmol), 5′-amino-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid amide (which was the product from the catalytic hydrogenation of 5′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid amide: 2.93 g, 12.6 mmol, 200 mL EtOH/THF/EtOAc mixture, 50 psi H2, 7 hr, with 300 mg of Pd/C 10%), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.89 g, 15.1 mmol) and DMAP (catalytic) in anhydrous DMF (25 mL) was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (400 mL) and washed with aqueous ammonium chloride (saturated, 200 mL), sodium bicarbonate (saturated, 200 mL with addition of brine to clear emulsion) and brine (100 mL). The aqueous ammonium chloride was extracted with ethyl acetate (200 mL) which was subsequently washed with brine (100 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and tritrated from boiling ethyl acetate to give 5′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid amide (1.5 g, 26%) as a light brown solid. LCMS calcd for C22H20F3N5O3 (m/e) 459, obsd 460 (M+H).

後処理

  1. washwashed with aqueous ammonium chloride (saturated, 200 mL), sodium bicarbonate (saturated, 200 mL with addition of brine to clear emulsion) and brine (100 mL)
  2. extractionThe aqueous ammonium chloride was extracted with ethyl acetate (200 mL) which
  3. washwas subsequently washed with brine (100 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-6341136ca9954df48c7c6cf2f3464463
出典データセット
uspto-grants-2012_04
特許番号
US08153644B2

反応ノート

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