Dimethylformamide → 2-(5,6-dimethoxypyridin-3-yl)-7-methoxy-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

HRID 1259347노트

반응식

HRID 1259347 반응식
Cl[C:2]1[N:7]=[C:6]2[CH:8]([O:22][CH3:23])[N:9]([C:12]3[CH:13]=[N:14][N:15]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH:16]=3)[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[C:31]([O:32][CH3:33])=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][N:27]=1.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:33][O:32][C:31]1[CH:30]=[C:29]([C:2]2[N:7]=[C:6]3[CH:8]([O:22][CH3:23])[N:9]([C:12]4[CH:13]=[N:14][N:15]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH:16]=4)[C:10](=[O:11])[C:5]3=[CH:4][CH:3]=2)[CH:28]=[N:27][C:26]=1[O:25][CH3:24]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 453617702,3-Dimethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 866619692-chloro-7-methoxy-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

생성물 1

HCID 667433492-(5,6-dimethoxypyridin-3-yl)-7-methoxy-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

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온도
110 °C

실험 절차

As shown in step 17-v of Scheme 17, to Compound 2058 (293 mg, 0.85 mmol), 2,3-dimethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (269 mg, 1.01 mmol), Na2CO3 (179 mg, 1.69 mmol), and Pd(PPh3)4 (98 mg, 0.085 mmol) was added DMF (10 mL), followed by the addition of water (2 mL). The reaction vessel was evacuated, placed under an atmosphere of nitrogen, then warmed to 110° C. (sand bath). After 16 hours the reaction mixture was partitioned between EtOAc and water (100 mL each). The organics were washed with water (70 mL), brine (70 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was dissolved/suspended in EtOAc (7 mL) and heated with swirling in a water bath at 50° C. for 40 minutes. The resulting mixture was treated with hexanes (5 mL) and swirled an additional 5 minutes at 50° C. After cooling to 23° C., the resulting solid was collected by filtration and washed with 1:1 (EtOAc:hexanes, 5 mL) to give 2-(5,6-dimethoxypyridin-3-yl)-7-methoxy-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (Compound 256) as a mixture of enantiomers: ESMS (M+H) 450.44; 1H NMR (CDCl3, 300 MHz) δ 8.57 (d, J=3 Hz, 1H), 8.35 (s, 1H), 8.27 (s, 2H), 7.99 (d, J=3 Hz, 1H), 7.93 (s, 1H), 6.40 (s, 1H), 5.22 (q, J=9 Hz, 2H), 3.96 (s, 3H), 3.93 (s, 3H), 3.13 (s, 3H).

후처리

  1. customThe reaction vessel was evacuated
  2. customAfter 16 hours the reaction mixture was partitioned between EtOAc and water (100 mL each)
  3. washThe organics were washed with water (70 mL), brine (70 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. temperatureheated
  8. additionThe resulting mixture was treated with hexanes (5 mL)
  9. waitswirled an additional 5 minutes at 50° C
  10. temperatureAfter cooling to 23° C.
  11. filtrationthe resulting solid was collected by filtration
  12. washwashed with 1:1 (EtOAc:hexanes, 5 mL)

출처 및 근거

ORD 기록
ord-35652fed2cd14cd5b438bb6ffad87e55
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08466288B2

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