Triethylamine → Tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate

HRID 72500ノート

反応式

HRID 72500 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([CH:32]=[CH:33][CH:34]=2)[O:17][CH:18]2[CH2:21][N:20]([C:22]3[N:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:23]=3[C:24](O)=[O:25])[CH2:19]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:59][C:60]1([C:63]2[CH:72]=[CH:71][C:66]([C:67]([O:69][CH3:70])=[O:68])=[CH:65][CH:64]=2)[CH2:62][CH2:61]1.C(N(CC)CC)C>CN(C)C=O.O>[Cl:31][C:28]1[CH:27]=[C:23]([C:24](=[O:25])[NH:59][C:60]2([C:63]3[CH:72]=[CH:71][C:66]([C:67]([O:69][CH3:70])=[O:68])=[CH:65][CH:64]=3)[CH2:62][CH2:61]2)[C:22]([N:20]2[CH2:21][CH:18]([O:17][C:16]3[CH:15]=[C:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]4)[CH:34]=[CH:33][CH:32]=3)[CH2:19]2)=[N:30][CH:29]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679581532-(3-(3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid

生成物 1

HCID 67958770Tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate収率 66.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A suspension of 2-(3-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid (D110) (150 mg, 0.306 mmol), 1-Hydroxybenzotriazole hydrate (47 mg, 0.306 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (88 mg, 0.46 mmol) in dimethylformamide (2 ml) was stirred 40 min at room temperature. A solution of methyl 4-(1-aminocyclopropyl)benzoate (D7) (68.9 mg, 0.306 mmol) and triethylamine (0.042 ml, 0.306 mmol) in dimethylformamide (2 ml) was added and the resulting mixture was stirred 40 min at room temperature. Water (2 ml) was added and the resulting precipitate was collected by filtration and purified by Biotage column (10 g) eluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20. Collected fractions, after solvent evaporation, afforded tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate (135 mg)

後処理

  1. stirringthe resulting mixture was stirred 40 min at room temperature
  2. filtrationthe resulting precipitate was collected by filtration
  3. custompurified by Biotage column (10 g)
  4. washeluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20
  5. customCollected fractions, after solvent evaporation

出典と根拠

ORDレコード
ord-6fc46c660ee24f5595393423087354ea
出典データセット
uspto-grants-2014_09
特許番号
US08828987B2

反応ノート

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