Water → 6-{4-[(Dimethylamino)sulfonyl]phenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1522387ノート

反応式

HRID 1522387 の反応式
Cl[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=1.[CH3:28][N:29]([CH3:48])[S:30]([C:33]1[CH:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][CH:34]=1)(=[O:32])=[O:31].C(=O)(O)[O-].[Na+].O>COCCOC.O>[CH3:28][N:29]([CH3:48])[S:30]([C:33]1[CH:34]=[CH:35][C:36]([C:2]2[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]3[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])=[O:16])[C:5]3[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=3[N:7]=2)=[CH:37][CH:38]=1)(=[O:31])=[O:32]

参加物

6

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 3868489N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1-sulfonamideHCID 565974266-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

生成物 1

HCID 680792336-{4-[(Dimethylamino)sulfonyl]phenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide収率 81.4%

試薬・触媒・溶媒 1

HCID 18180031Water 1,2-dimethoxyethane溶媒

実験手順

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (75 mg, 0.19 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (90 mg, 0.29 mmol) in DME/water (3 ml:1 ml). PdCl2 (dppf)-CH2Cl2 adduct (7.9 mg, 0.009 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (48.7 mg, 0.58 mmol) was added, the vessel was sealed, and the reaction mixture was irradiated (microwave) at 150° C. for 30 min. After cooling, 2 mL of water was added and solids that precipitated were filtered. DCM/MeOH (1:1) was added, the mixture was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with EtOH/EtOAc (1:1), the solids filtered and washed with EtOAc and DCM, and then dried to afford the title compound (83 mg, 78%) as a white solid. LCMS E-S (M+H)=537.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1 H) 8.79 (t, J=4.93 Hz, 1 H) 8.47 (m, J=8.59 Hz, 2 H) 7.90 (m, J=8.59 Hz, 2 H) 7.80 (s, 1 H) 5.89 (s, 1 H) 5.28 (quin, J=6.69 Hz, 1 H) 4.40 (d, J=5.05 Hz, 2 H) 2.66 (s, 6 H) 2.47 (s, 3 H) 2.25 (s, 3 H) 2.12 (s, 3 H) 1.53 (s, 3 H) 1.51 (s, 3 H).

後処理

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. customthe reaction mixture was irradiated (microwave) at 150° C. for 30 min
  5. temperatureAfter cooling
  6. customsolids that precipitated
  7. filtrationwere filtered
  8. additionDCM/MeOH (1:1) was added
  9. customthe mixture was pre-absorbed on silica gel
  10. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  11. additionThe isolated product was treated with EtOH/EtOAc (1:1)
  12. filtrationthe solids filtered
  13. washwashed with EtOAc and DCM
  14. customdried

出典と根拠

ORDレコード
ord-9400521e4d7d4d7c8768c14bdf979acb
出典データセット
uspto-grants-2015_07
特許番号
US09073924B2

反応ノート

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