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

HRID 2169620Notes

Reaction equation

HRID 2169620 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]=[CH:33]2>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]=[CH:33]2

Participants

6

Reactant 2

HCID 681948917-fluoro-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 601979832-(7-fluoro-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, 90 mg, 0.228 mmol), 7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (119 mg, 0.456 mmol) and PdCl2(dppf) (8.34 mg, 0.011 mmol) in dioxane (2.5 mL) and aqueous saturated NaHCO3 (0.5 mL). 1H NMR (400 MHz, DMSO-d6) δ 3.22 (m, 3 H), 3.24-3.36 (m, 2 H), 3.39-3.75 (m, 3 H), 3.88-4.06 (m, 2 H), 4.06-4.16 (m, 1 H), 4.62-4.77 (m, 2 H), 7.05-7.21 (m, 2 H), 7.45-7.53 (m, 1 H), 7.55-7.62 (m, 1 H), 7.62-7.72 (m, 3 H), 7.90-7.97 (m, 2 H), 11.85-12.09 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C25H24FN5O3S, 494.16; found 494.5.

Sources & evidence

ORD record
ord-489aa83653fe43999de189ee3e2ccb17
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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