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Stannanecarbonitrile, tributyl- → 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile

HRID 1618771
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HRID 1618771 반응식
Br[C:2]1[N:7]=[C:6]2[C:8]([CH3:30])([CH3:29])[CH2:9][N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[C:5]2=[CH:4][C:3]=1[N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C([Sn]([C:50]#[N:51])(CCCC)CCCC)CCC>CN1C(=O)CCC1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[F:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([N:10]3[C:5]4[C:6](=[N:7][C:2]([C:50]#[N:51])=[C:3]([N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)[CH:4]=4)[C:8]([CH3:29])([CH3:30])[CH2:9]3)=[C:12]([CH3:28])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[N:14]2)=[CH:19][CH:18]=1
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참가 물질

5

반응물 2

HCID 200512Stannanecarbonitrile, tributyl-HCID 866642814-(5-bromo-3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline

생성물 1

HCID 509394701-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile

시약·촉매·용매 2

HCID 54751079XPhos Palladacycle
촉매
HCID 13387N-methyl-2-pyrrolidone용매

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온도
140 °C

실험 절차

To a stirred solution of 4-(5-bromo-3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline (61 mg, 0.111 mmol) in NMP (1.5 mL) was added tri-n-butyltin cyanide (35.2 mg, 0.111 mmol), XPhos precatalyst (16.3 mg, 0.022 mmol) and heated at 140° C. for 2 h in the microwave. After this time the reaction was partitioned between EtOAc (60 mL) and water (30 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Purification by reverse phase HPLC (10 to 60% acetonitrile water) gave 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile. 1H NMR (400 MHz, chloroform-d) δ ppm 8.68-8.80 (1H, m), 7.84-7.99 (3H, m), 7.67 (1H, dd, J=9.2, 5.9 Hz), 7.44 (1H, ddd, J=6.9, 4.9, 1.9 Hz), 7.35 (1H, ddd, J=9.2, 8.0, 2.5 Hz), 5.74 (1H, s), 3.87 (2H, s), 3.79 (4H, t, J=4.7 Hz), 2.94-3.11 (4H, m), 2.40 (3H, s), 1.59 (3H, s), 1.53 (3H, s). Mass Spectrum (ESI) m/e=495.0 (M+1).

후처리

  1. customAfter this time the reaction was partitioned between EtOAc (60 mL) and water (30 mL)
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customPurification by reverse phase HPLC (10 to 60% acetonitrile water)

출처 및 근거

ORD 기록
ord-95710f8a862a42688d81c2ad1527ea20
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08765940B2

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