Triethylamine → 3-(1-cyanocyclopropyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide

HRID 2190401ノート

反応式

HRID 2190401 の反応式
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]5([C:29]#[N:30])[CH2:28][CH2:27]5)[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl.Cl.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42](O)=[O:43])[CH2:37][CH2:36]1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.CO>[C:29]([C:26]1([C:22]2[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=2)[C:19]([NH:18][C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([O:11][C:9]3[CH:8]=[CH:7][C:5]4[N:6]=[C:2]([NH:1][C:42](=[O:43])[CH2:41][N:38]5[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]5)[S:3][C:4]=4[CH:10]=3)[CH:13]=2)=[O:31])[CH2:27][CH2:28]1)#[N:30]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 448914242-(4-Methylpiperazin-1-yl)acetic acid dihydrochloride2 回HCID 86655364N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide

生成物 1

HCID 251962243-(1-cyanocyclopropyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide収率 24%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒HCID 1049Pyridine溶媒

実験手順

To a solution of N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide (436 mg, 1.02 mmol) produced in Example A15(iii) in pyridine (10 mL) were added (4-methylpiperazin-1-yl)acetic acid dihydrochloride (278 mg, 1.20 mmol), N,N-dimethylpyridine-4-amine (79.3 mg, 649 μmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (470 mg, 2.45 mmol) at room temperature, and the mixture was stirred at room temperature for 14 hr. To the reaction mixture were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (454 mg, 2.37 mmol), (4-methylpiperazin-1-yl)acetic acid dihydrochloride (281 mg, 1.22 mmol), and triethylamine (10 mL) and the mixture was further stirred for 4 hr. To the reaction mixture was added methanol (10 mL) and the mixture was stirred at room temperature for 30 min and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL), washed with saturated aqueous ammonium chloride solution (80 mL×2) and saturated aqueous sodium hydrogencarbonate solution (50 mL), successively, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→90/10) and crystallized from ethyl acetate and hexane to give the title compound (136 mg, 24%) as colorless crystals.

後処理

  1. stirringthe mixture was further stirred for 4 hr
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with ethyl acetate (100 mL)
  5. washwashed with saturated aqueous ammonium chloride solution (80 mL×2) and saturated aqueous sodium hydrogencarbonate solution (50 mL)
  6. dry with materialsuccessively, and dried over anhydrous magnesium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→90/10)
  10. customcrystallized from ethyl acetate and hexane

出典と根拠

ORDレコード
ord-1906d86499d843e6ad871a19c8a44cf0
出典データセット
uspto-grants-2012_12
特許番号
US08324395B2

反応ノート

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