Sodium Carbonate → 3-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

HRID 85023노트

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HRID 85023 반응식
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[NH:16][CH:15]=[CH:14]4)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[CH3:30][O:31][C:32]1[CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:44]=[CH:43][C:33]=1[O:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>CC#N.CO.CC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:16]1[C:17]2[C:13](=[CH:12][C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:45]5[CH:44]=[CH:43][C:33]([O:34][CH2:35][CH2:36][N:37]6[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]6)=[C:32]([O:31][CH3:30])[CH:46]=5)[CH:3]=4)[NH:8][CH:9]=3)=[CH:19][CH:18]=2)[CH:14]=[CH:15]1

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 667791765-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine2회HCID 667799091-(2-(2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine

생성물 1

HCID 462345053-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 180Acetone용매HCID 887Methanol용매HCID 6342Acetonitrile용매

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온도
150 °C

실험 절차

To a solution of 5-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Intermediate B) (92 mg, 0.20 mmol) in CH3CN (2 mL) in a Personal Chemistry microwave reaction vial was added 1-(2-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine (Intermediate AM) (72 mg, 0.20 mmol), bis(triphenylphosphine)-palladium(II) dichloride (20 mg, 0.028 mmol), and 1 M Na2CO3 (2 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 25 min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and concentrated in vacuo to give Intermediate AN. The residue was dissolved in MeOH (3 mL) and acetone (2 mL), and 2 M NaOH (1.5 mL) was added. The resulting mixture was stirred at 50° C. for 2 h, after which it was partitioned between EtOAc and 1 M NaOH. The organic layer was separated, dried over MgSO4, filtered, and stripped to give a residue that was subjected to preparatory HPLC to yield the title compound. HPLC retention time: 1.29 minutes; MS ESI (m/z) 468.6 (M+1)+, calc. 467.

후처리

  1. customThe resulting mixture was de-gassed with Ar for 10 min
  2. customThe organic layer was separated
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give Intermediate AN
  6. customafter which it was partitioned between EtOAc and 1 M NaOH
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customto give a residue that

출처 및 근거

ORD 기록
ord-4b44ab4837d94020b62dc578e5ac54d2
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846909B2

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