3-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea → 1-(4-(5-(1-(4-Chlorophenyl)cyclopropyl)-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylurea

HRID 1631798Notes

Reaction equation

HRID 1631798 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=4)[CH2:14][CH2:13]3)[C:7](=[O:22])[CH:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[CH3:27][NH:28][C:29]([NH:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)=[O:30]>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]>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C:12]2([N:8]3[C:7](=[O:22])[CH:6]4[CH2:23][O:24][CH2:25][CH2:26][N:5]4[C:4]4[N:3]=[C:2]([C:35]5[CH:34]=[CH:33][C:32]([NH:31][C:29]([NH:28][CH3:27])=[O:30])=[CH:37][CH:36]=5)[N:11]=[CH:10][C:9]3=4)[CH2:14][CH2:13]2)=[CH:16][CH:17]=1

Participants

6

Reactant 2

HCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 866701122-chloro-5-(1-(4-chlorophenyl)cyclopropyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 681950631-(4-(5-(1-(4-Chlorophenyl)cyclopropyl)-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylurea

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 84 using 2-chloro-5-(1-(4-chlorophenyl)cyclopropyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x36, 100 mg, 0.256 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (141 mg, 0.511 mmol), and PdCl2(dppf) (18.70 mg, 0.026 mmol) in dioxane (2 mL) and aqueous saturated NaHCO3 (0.4 mL). 1H NMR (400 MHz, DMSO-d6) δ 1.10-1.24 (m, 2H), 1.46-1.60 (m, 2H), 2.54-2.60 (d, 3H), 2.84-3.03 (m, 1H), 3.46-3.57 (m, 2H), 3.91-4.00 (m, 1H), 4.08-4.20 (m, 1H), 4.33-4.55 (m, 2H), 5.98-6.07 (m, 1H), 7.01-7.17 (m, 2H), 7.23-7.34 (m, 2H), 7.36-7.46 (m, 2H), 7.68-7.73 (m, 1H), 8.02-8.13 (m, 2H), 8.61-8.70 (m, 1H). ESI-MS m/z [M+H]+ calc'd for C26H25ClN6O3, 505.17. found 505.4.

Sources & evidence

ORD record
ord-15649ba8a1a34d648bd27ae4cf95602d
Source dataset
uspto-grants-2014_07
Patent number
US08791107B2

Reaction notes

Loading…