Triethylamine → N-(4-Fluorophenyl)-N'-(4-{[2-({[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide

HRID 2066226ノート

反応式

HRID 2066226 の反応式
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][C:38]([C:40]2([C:43](O)=[O:44])[CH2:42][CH2:41]2)=[O:39])=[CH:33][CH:32]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[F:30][C:31]1[CH:32]=[CH:33][C:34]([NH:37][C:38]([C:40]2([C:43]([NH:1][C:2]3[CH:29]=[CH:28][C:5]([O:6][C:7]4[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]5[CH2:17][CH2:18][CH:19]([CH2:22][N:23]6[CH2:27][CH2:26][CH2:25][CH2:24]6)[CH2:20][CH2:21]5)=[O:15])[CH:8]=4)=[CH:4][CH:3]=3)=[O:44])[CH2:42][CH2:41]2)=[O:39])=[CH:35][CH:36]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 59596970N-[4-(4-aminophenoxy)-2-pyridinyl]-4-(1-pyrrolidinylmethyl)-1-piperidinecarboxamide

生成物 1

HCID 59596909N-(4-Fluorophenyl)-N'-(4-{[2-({[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide収率 63.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

4-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (125 mg) was dissolved in N,N-dimethylformamide (2 ml), and 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylic acid (176 mg), triethylamine (0.11 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (349 mg) were added thereto in this order at room temperature, followed by stirring for 1 hr. Liquid-liquid separation was carried out after addition of ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate to the reaction mixture. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:5, then ethyl acetate). The solvent was concentrated under reduced pressure, and the resultant residue was suspended in diethyl ether (4 ml) and hexane (4 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (121.2 mg, 63.8%).

後処理

  1. customat room temperature
  2. customLiquid-liquid separation
  3. additionafter addition of ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe solvent was concentrated under reduced pressure
  7. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  8. concentrationThe solvent was concentrated under reduced pressure
  9. filtrationThe solid was collected by filtration
  10. customdried under aeration

出典と根拠

ORDレコード
ord-bfa12b5b690b4dfa90bed9a35a1bdfe0
出典データセット
uspto-grants-2012_10
特許番号
US08288538B2

反応ノート

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