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Dichloromethane → 3-Methoxy-4-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzoic acid

HRID 1027164
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HRID 1027164 반응식
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:19])[CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)=[CH:4][CH:3]=1.B([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][C:24]=1[O:32][CH3:33])(O)O.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O.CCOCC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[CH3:33][O:32][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:23]=1[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:19])[CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)=[CH:4][CH:3]=1)[C:27]([OH:29])=[O:28]
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참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 231342764-Borono-3-methoxybenzoic acidHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2회

생성물 1

HCID 867105563-Methoxy-4-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzoic acid

시약·촉매·용매 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 962Water용매2회
HCID 3283Diethyl Ether용매
HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

To a microwave vial was added 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 1-1, 100 mg, 0.35 mmol), 4-borono-3-methoxybenzoic acid (76 mg, 0.39 mmol), PdCl2(dppf).CH2Cl2 (29 mg, 0.035 mmol), Na2CO3 (112 mg, 1.06 mmol), DMF (2 mL) and water (0.5 mL). The microwave vial was sealed and heated in a microwave at 120° C. for 45 min. The crude reaction mixture was cooled and diluted in water and ether. The aqueous layer was extracted with ether. The resultant emulsion was diluted in water and 1 M NaOH. The aqueous layer was acidified with 1 M HCl slowly and extracted again with ether. The organic layer was concentrated under reduced pressure, and the resulting precipitate was suspended in 10 mL MeOH and filtered. The filtrate was concentrated and used without further purification. LCMS Rt=0.63 min (condition B); MS (M+1)=399.0

후처리

  1. customThe microwave vial was sealed
  2. customThe crude reaction mixture
  3. temperaturewas cooled
  4. extractionThe aqueous layer was extracted with ether
  5. additionThe resultant emulsion was diluted in water
  6. extractionextracted again with ether
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. customused without further purification

출처 및 근거

ORD 기록
ord-667e7c1fe362406597737c664f7e9bb2
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729263B2

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