7-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole → 2-(7-fluoro-3-methyl-1H-indol-4-yl)-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 2169619Notes

Reaction equation

HRID 2169619 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[CH2:7][CH:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[F:27][C:28]1[CH:29]=[CH:30][C:31](B2OC(C)(C)C(C)(C)O2)=[C:32]2[C:36]=1[NH:35][CH:34]=[C:33]2[CH3:37]>O1CCOCC1.C([O-])(O)=O.[Na+].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:27][C:28]1[CH:29]=[CH:30][C:31]([C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH2:12][C:13]4[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=4)[CH2:7][CH:6]4[CH2:23][O:24][CH2:25][CH2:26][N:5]4[C:4]=3[N:3]=2)=[C:32]2[C:36]=1[NH:35][CH:34]=[C:33]2[CH3:37]

Participants

6

Reactant 2

HCID 681953757-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 866700922-Chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Product 1

HCID 601978772-(7-fluoro-3-methyl-1H-indol-4-yl)-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

The title compound was prepared in a manner similar to EXAMPLE 2 using 2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x9, 66.0 mg, 0.167 mmol), 7-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (92 mg, 0.334 mmol) and PdCl2(dppf) (9.79 mg, 0.013 mmol) in dioxane (1 mL) and aqueous saturated NaHCO3 (0.2 mL). 1H NMR (400 MHz, DMSO-d6) δ 1.93-2.07 (m, 3 H), 2.89-2.99 (m, 1 H), 3.21-3.34 (m, 6 H), 3.47-3.49 (m, 1 H), 3.67-3.72 (m, 1 H), 3.86-3.99 (m, 2 H), 4.35-4.44 (m, 1 H), 4.57-4.64 (m, 2 H), 6.83-6.91 (m, 1 H), 7.02-7.08 (m, 1 H), 7.11-7.17 (m, 1 H), 7.58-7.66 (m, 3 H), 7.87-7.96 (m, 2 H), 11.23-11.30 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C26H26FN5O3S, 508.17; found 508.5.

Sources & evidence

ORD record
ord-9dfbab22c012407083d912953a5224cd
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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