Potassium Phosphate, Tribasic → 2-(2,2-difluorocyclopropyl)-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 595587Notes

Reaction equation

HRID 595587 reaction equation
[F:1][C:2]1([F:33])[CH2:4][CH:3]1[C:5]1[O:6][C:7]2[CH:17]=[C:16]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])[C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:8]=2[C:9]=1[C:10]([NH:12][CH3:13])=[O:11].Cl[C:35]1[CH:36]=[CH:37][C:38]2[O:51][CH2:50][N:41]3[C:42]4[CH:43]=[CH:44][CH:45]=[C:46]([F:49])[C:47]=4[CH:48]=[C:40]3[C:39]=2[N:52]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:33][C:2]1([F:1])[CH2:4][CH:3]1[C:5]1[O:6][C:7]2[CH:17]=[C:16]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:20])=[O:21])[C:15]([C:35]3[CH:36]=[CH:37][C:38]4[O:51][CH2:50][N:41]5[C:42]6[CH:43]=[CH:44][CH:45]=[C:46]([F:49])[C:47]=6[CH:48]=[C:40]5[C:39]=4[N:52]=3)=[CH:14][C:8]=2[C:9]=1[C:10]([NH:12][CH3:13])=[O:11]

Participants

8

Reactant 4

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 903335432-(2,2-difluorocyclopropyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Product 1

HCID 778460712-(2,2-difluorocyclopropyl)-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-carboxamideYield 8.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(2,2-difluorocyclopropyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (20 mg, 0.04 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (11 mg, 0.04 mmol), Pd2(dba)3 (10 mg, 0.01 mmol), X-Phos (10 mg, 0.02 mmol) and K3PO4 (60 mg, 0.12 mmol) in DMF (2 mL) was stirred at 100° C. for 6 h. Water was added and the mixture was extracted with EtOAc. After concentration, the residue was purified by prep-TLC (PE:EA=1:3) to give the product of 2-(2,2-difluorocyclopropyl)-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 (2 mg, yield: 8%). 1H-NMR (MeOD, 400 MHz) δ 8.00 (s, 1H), 7.83 (s, 1H), 7.60 (s, 2H), 7.32 (d, J=8.4 Hz, 1H), 7.26˜7.20 (m, 2H), 6.93 (dd, J=8.0, 10.4 Hz, 1H), 6.11 (s, 2H), 3.64˜3.56 (m, 1H), 3.34 (s, 3H), 2.99 (s, 3H), 2.98 (s, 3H), 2.26˜2.17 (m, 2H). MS (M+H)+: 597.

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. concentrationAfter concentration
  3. customthe residue was purified by prep-TLC (PE:EA=1:3)

Sources & evidence

ORD record
ord-9298e1158c6144b09035217eceb15c19
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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