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

HRID 2169623Notes

Reaction equation

HRID 2169623 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.CC1(C)C(C)(C)OB([C:35]2[CH:43]=[CH:42][CH:41]=[C:40]3[C:36]=2[CH:37]=[C:38]([C:44]([F:47])([F:46])[F:45])[NH:39]3)O1>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]>[CH3:22][S:19]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:8]2[CH2:7][CH:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]3[N:3]=[C:2]([C:35]4[CH:43]=[CH:42][CH:41]=[C:40]5[C:36]=4[CH:37]=[C:38]([C:44]([F:47])([F:46])[F:45])[NH:39]5)[N:11]=[CH:10][C:9]2=3)=[CH:14][CH:15]=1)(=[O:21])=[O:20]

Participants

6

Reactant 2

HCID 591513374-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)-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 601976575-(4-(methylsulfonyl)benzyl)-2-(2-(trifluoromethyl)-1H-indol-4-yl)-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 3 using 2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x9, 63.5 mg, 0.161 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)-1H-indole (100 mg, 0.321 mmol) and PdCl2(dppf) (5.88 mg, 8.04 mmol) in dioxane (2 mL) and aqueous saturated NaHCO3 (0.4 mL). 1H NMR (400 MHz, DMSO-d6) δ 3.21 (m, 3 H), 3.23-3.34 (m, 3 H), 3.56-3.66 (m, 2 H), 3.88-4.03 (m, 2 H), 4.05-4.16 (m, 1 H), 4.59-4.68 (m, 1 H), 4.71 (s, 2 H), 7.41-7.48 (m, 1 H), 7.56 (s, 2 H), 7.65 (d, J=8.34 Hz, 3 H), 7.79-7.86 (m, 1 H), 7.94 (d, J=8.34 Hz, 2 H), 12.56-12.65 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C26H24F3N5O3S, 544.16; found 544.5.

Sources & evidence

ORD record
ord-6dea955ad7ab49afabedefecc2cb5c8b
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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