Sodium Carbonate → 2,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 2389007노트

반응식

HRID 2389007 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1.[F:35][C:36]1[C:46]([F:47])=[CH:45][C:44](I)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39].C(=O)([O-])[O-].[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C(#N)C>[F:35][C:36]1[C:46]([F:47])=[CH:45][C:44]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])[C:12]3=[N:13][CH:14]=2)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]

참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 579757722,3-difluoro-5-iodo-N,N-dimethyl-benzamideHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

생성물 1

HCID 579757282,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide수율 68%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (3.1 g, 6.43 mmol), 2,3-difluoro-5-iodo-N,N-dimethyl-benzamide (2 g, 6.43 mmol) and 1,1′-bis(diphenylphosphino)-ferrocenepalladium(II)-dichloride dichlormethane adduct (262 mg, 0.32 mmol) in acetonitrile (14 mL) and aqueous solution of sodium carbonate (2M, 6.5 mL) was irradiated in a Personal Chemistry Optimizer at 100° C. for 15 min. Sodium sulfate was added to the crude reaction mixture and the solids were filtered over Celite. The solids were washed with acetonitrile and the combined filtrate was concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded 1.23 g (4.37 mmol, 68%) of 2,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J=2.5 Hz, 1H), 8.46 (d, J=2 Hz, 1H), 8.02 (ddd, J1=12 Hz, J2=10 Hz, J3=2.5 Hz, 1H), 7.67 (m, 1H), 7.61 (dd, J1=8 Hz, J2=1.5 Hz, 1H), 7.49 (m, 1H), 7.23 (d, J=8 Hz, 1H), 7.10 (td, J1=8 Hz, J2=1 Hz, 1H), 5.84 (s, 2H), 3.81 (s, 3H), 3.68 (t, J=8 Hz, 2H), 3.02 (s, 3H), 2.91 (s, 3H), 0.85 (t, J=8 Hz, 2H), −0.09 (s, 9H). MS: m/z 539 [MH+]

후처리

  1. customwas irradiated in a Personal Chemistry Optimizer at 100° C. for 15 min
  2. customreaction mixture
  3. filtrationthe solids were filtered over Celite
  4. washThe solids were washed with acetonitrile
  5. concentrationthe combined filtrate was concentrated
  6. customPurification by flash silica gel chromatography

출처 및 근거

ORD 기록
ord-836bee3acdf04b03b78dd34a2a234e02
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268994B2

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