Pyridine → 3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-pyrazin-2-yl-benzamide

HRID 600517ノート

反応式

HRID 600517 の反応式
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][N:34]([CH3:37])[C:33]4=[O:38])[CH:30]=3)[C:25]([OH:27])=O)=[CH:17][CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:39][C:40]1[CH:45]=[N:44][CH:43]=[CH:42][N:41]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][N:34]([CH3:37])[C:33]4=[O:38])[CH:30]=3)[C:25]([NH:39][C:40]3[CH:45]=[N:44][CH:43]=[CH:42][N:41]=3)=[O:27])=[CH:17][CH:16]=2)=[O:14])[CH2:10][CH2:11][CH2:12]1

参加物

6

反応物 4

HCID 1049PyridineHCID 78747AminopyrazineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 597611453-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid2 回

生成物 1

HCID 249526643-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-pyrazin-2-yl-benzamide収率 22%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.08 0 mL, 0.60 mmol) was added to a solution of 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid (Intermediate 30) (202 mg, 0.49 mmol) in DCM (5 mL) and stirred at ambient temperature for 50 minutes. 2-Amino-pyrazine (CAS no. 5049-61-6) (94 mg, 0.98 mmol) and pyridine (0.80 mL, 0.98 mmol) were added and the reaction stirred for 16 hours. The solvent was removed under reduced pressure and the residue taken up in ethyl acetate (40 mL), washed with saturated sodium bicarbonate (20 mL), water (10 mL), and brine (10 mL), dried (MgSO4) and evaporated under reduced pressure to give the crude product. The residue was purified by chromatography on silica, eluting with a gradient of 0-4% methanol in DCM to give product (53 mg, 22%). 1H NMR δ300 MHz, CDCl3) 2.13-2.27 (m, 1H), 2.35 (quintet, 2H), 2.52-2.67 (m, 1H), 2.93 (s, 3H), 3.34-3.59 (m, 2H), 4.24 (t, 2H), 4.70 (t, 2H), 4.94 (t, 1H), 6.98 (s, 1H), 7.23 (s, 1H), 7.39 (d, 1H), 7.48 (s, 1H), 8.12 (d, 1H), 8.27 (q, 1H), 8.33 (d, 1H), 8.39 (d, 1H), 8.66 (s, 1H), 9.66 (s, 1H); m/z 489 (M+H)+.

後処理

  1. stirringthe reaction stirred for 16 hours
  2. customThe solvent was removed under reduced pressure
  3. washwashed with saturated sodium bicarbonate (20 mL), water (10 mL), and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated under reduced pressure
  6. customto give the crude product
  7. customThe residue was purified by chromatography on silica
  8. washeluting with a gradient of 0-4% methanol in DCM

出典と根拠

ORDレコード
ord-dc92d46251a44bbdab552e89d1f7d4f1
出典データセット
uspto-grants-2011_03
特許番号
US07902200B2

反応ノート

読み込み中…