Acetic Acid → propane-1-sulfonic acid {2,4-difluoro-3-[5-(1-pyrimidin-2-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide

HRID 60105

반응식

HRID 60105 반응식
ClC1C=CC=C(Cl)C=1C([N:6]1[C:10]2=[N:11][CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=[C:9]2[C:8]([C:24]([C:26]2[C:27]([F:40])=[C:28]([NH:33][S:34]([CH2:37][CH2:38][CH3:39])(=[O:36])=[O:35])[CH:29]=[CH:30][C:31]=2[F:32])=[O:25])=[CH:7]1)=O.Br[C:47]1[CH:48]=[N:49][N:50]([C:52]2[N:57]=[CH:56][CH:55]=[CH:54][N:53]=2)[CH:51]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>C(#N)C.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]>[F:40][C:27]1[C:26]([C:24]([C:8]2[C:9]3[C:10](=[N:11][CH:12]=[C:13]([C:47]4[CH:48]=[N:49][N:50]([C:52]5[N:57]=[CH:56][CH:55]=[CH:54][N:53]=5)[CH:51]=4)[CH:14]=3)[NH:6][CH:7]=2)=[O:25])=[C:31]([F:32])[CH:30]=[CH:29][C:28]=1[NH:33][S:34]([CH2:37][CH2:38][CH3:39])(=[O:36])=[O:35]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 457897012-(4-Bromo-1H-pyrazol-1-yl)pyrimidineHCID 58368752propane-1-sulfonic acid {3-[1-(2,6-dichloro-benzoyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

생성물 1

HCID 53262160propane-1-sulfonic acid {2,4-difluoro-3-[5-(1-pyrimidin-2-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6342Acetonitrile용매

실험 절차

To a solution of propane-1-sulfonic acid {3-[1-(2,6-dichloro-benzoyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide (32, 18 mg, 0.026 mmol) and 2-(4-bromo-pyrazol-1-yl)-pyrimidine (33, 4.95 mg, 0.022 mmol) in 800 μL of acetonitrile is added 400 μL of 1M aqueous potassium carbonate and approximately 1-2 mg of [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium (II) (PdCl2 dppf). The reaction mixture is microwave irradiated at 145° C. for 15 minutes, then neutralized with acetic acid, and extracted with 2×1 mL of ethyl acetate. The combined organic layer is concentrated under vacuum, the residue dissolved in 500 μL of dimethylsulfoxide and purified by HPLC using a C18 column, eluting with water/acetonitrile and 0.1% trifluoroacetic acid, 20-100% acetonitrile at 6 mL per minute. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound. MS (ESI) [M+H+]+=524.5.

후처리

  1. customThe reaction mixture is microwave irradiated at 145° C. for 15 minutes
  2. extractionextracted with 2×1 mL of ethyl acetate
  3. concentrationThe combined organic layer is concentrated under vacuum
  4. dissolutionthe residue dissolved in 500 μL of dimethylsulfoxide
  5. custompurified by HPLC
  6. washeluting with water/acetonitrile and 0.1% trifluoroacetic acid, 20-100% acetonitrile at 6 mL per minute
  7. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-8ea76c56de744cad9f961a8f8620b203
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440969B2

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