1,2-Dichloroethane → HCID 56599209, 화합물

HRID 1522509노트

반응식

HRID 1522509 반응식
[Br:1][C:2]1[C:10]2[C:9]([C:11]([OH:13])=O)=[CH:8][C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:6][C:5]=2[N:4]([CH:20]([CH3:22])[CH3:21])[N:3]=1.Cl.[NH2:24][CH2:25][C:26]1[C:27](=[O:34])[NH:28][C:29]([CH3:33])=[CH:30][C:31]=1[CH3:32].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.CN1CCOCC1.[Al].C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O.O>[Br:1][C:2]1[C:10]2[C:9]([C:11]([NH:24][CH2:25][C:26]3[C:27](=[O:34])[NH:28][C:29]([CH3:33])=[CH:30][C:31]=3[CH3:32])=[O:13])=[CH:8][C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:6][C:5]=2[N:4]([CH:20]([CH3:21])[CH3:22])[N:3]=1

참가 물질

11

반응물 8

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5359268AluminumHCID 438104513-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one hydrochlorideHCID 671241663-Bromo-1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

생성물 1

HCID 56599209HCID 56599209, 화합물

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

실험 절차

3-Bromo-1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (93 mg, 0.258 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone hydrochloride (64 mg, 0.336 mmol), HOBT (60 mg, 0.387 mmol) and EDC (74 mg, 0.387 mmol) were suspended in DMSO (14 mL) and stirred at room temperature for 10 minutes, after which time DIEA (0.9 ml, 5.16 mmol) was added. After stirring for 2 h, 4-methylmorpholine (1 ml, 9.04 mmol) was added. The reaction mixture was stirred first at room temperature for 21 h, and then at 80° C. (aluminum heating block) for 31 h. The reaction mixture was cooled to room temperature and then added dropwise to a cold, slightly basic solution (pH˜8-10) of water (100 mL) and 1N Na2CO3 (8 mL). After stirring for 20 min., the contents were extracted with EtOAc (2×100 mL). The combined organic layers are washed with brine, dried over Na2SO4, filtered, and concentrated to a residue. The crude residue was dissolved in 10% MeOH/DCM and purified by silica gel chromatography (eluent: 10-95% gradient EtOAc/Hexanes and then 10% (5% NH4OH/MeOH)/DCM and EtOAc, 10-90% gradient). The product was collected as an off-white solid. (35 mg, 27%). LCMS E-S (M+H)=494.1/496.0. 1H NMR (400 MHz, CHLOROFORM-d) δ 11.58 (br. s., 1H), 8.11 (dd, J=1.89, 7.71 Hz, 2H), 7.68 (br. s., 1H), 7.60 (br. s., 1H), 7.44-7.53 (m, 3H), 5.92 (s, 1H), 5.42 (quin, J=6.69 Hz, 1H), 4.63 (br. s., 1H), 2.41 (br. s., 3H), 2.11 (br. s., 3H), 1.62 (d, J=6.57 Hz, 6H).

후처리

  1. stirringAfter stirring for 2 h
  2. stirringThe reaction mixture was stirred first at room temperature for 21 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringAfter stirring for 20 min.
  5. extractionthe contents were extracted with EtOAc (2×100 mL)
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a residue
  10. dissolutionThe crude residue was dissolved in 10% MeOH/DCM
  11. custompurified by silica gel chromatography (eluent
  12. customThe product was collected as an off-white solid

출처 및 근거

ORD 기록
ord-b024301f38574b799232e81d363d548a
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073924B2

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