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 600517노트

반응식

HRID 600517 반응식
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

참가 물질

6

반응물 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 acid2회

생성물 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-benzamide수율 22%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-dc92d46251a44bbdab552e89d1f7d4f1
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902200B2

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