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Potassium Phosphate, Tribasic → 2-(bicyclo[3.1.0]hexan-1-yl)-5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595585
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HRID 595585 반응식
[C:1]12([C:7]3[O:8][C:9]4[CH:19]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:23])=[O:22])[C:17](B5OC(C)(C)C(C)(C)O5)=[CH:16][C:10]=4[C:11]=3[C:12]([NH:14][CH3:15])=[O:13])[CH2:6][CH:5]1[CH2:4][CH2:3][CH2:2]2.Cl[C:36]1[CH:37]=[CH:38][C:39]2[O:52][CH2:51][N:42]3[C:43]4[CH:44]=[CH:45][CH:46]=[C:47]([F:50])[C:48]=4[CH:49]=[C:41]3[C:40]=2[N:53]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O>[C:1]12([C:7]3[O:8][C:9]4[CH:19]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:22])=[O:23])[C:17]([C:36]5[CH:37]=[CH:38][C:39]6[O:52][CH2:51][N:42]7[C:43]8[CH:44]=[CH:45][CH:46]=[C:47]([F:50])[C:48]=8[CH:49]=[C:41]7[C:40]=6[N:53]=5)=[CH:16][C:10]=4[C:11]=3[C:12]([NH:14][CH3:15])=[O:13])[CH2:6][CH:5]1[CH2:4][CH2:3][CH2:2]2
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HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903335532-(bicyclo[3.1.0]hexan-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

생성물 1

HCID 77846000
2-(bicyclo[3.1.0]hexan-1-yl)-5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide
수율 16.6%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

To a degassed solution of 2-(bicyclo[3.1.0]hexan-1-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.20 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (67 mg, 0.24 mmol), K3PO4 (109 mg, 0.41 mmol) in 1,4-Dioxane (5 mL) and H2O (0.5 ml) was added Pd(dba)3 (5 mg), X-Phos (5 mg) under N2, then the mixture was stirred at 110° C. for 2 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O, brine, extracted with DCM, and dried over Na2SO4. After concentration, the residue was purified by prep-HPLC to give the product of 2-(bicyclo[3.1.0]hexan-1-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 16%). 1H-NMR (CDCl3, 400 MHz) δ 8.12 (s, 1H), 7.55 (s, 1H), 7.46 (s, 2H), 7.21 (s, 2H), 7.12 (d, J=8.0 Hz, 1H), 6.86 (q, J=8.0 Hz, 1H), 6.17 (d, J=4.0 Hz, 1H), 5.60 (s, 2H), 3.38 (s, 3H), 3.05 (d, J=4.8 Hz, 3H), 2.67 (s, 3H), 2.14˜2.22 (m, 2H), 2.11˜2.16 (m, 2H), 2.01˜2.09 (m, 2H), 1.91˜1.98 (m, 1H), 1.84 (d, J=4.0 Hz, 2H). MS (M+H)+: 601.

후처리

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. extractionextracted with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentration
  7. customthe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-4f8c5b1bf43a41c498e56a0ca1110b7a
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09242998B2

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