Sodium Bicarbonate → HCID 68194927, compound

HRID 2169655Notes

Reaction equation

HRID 2169655 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:7](=[O:18])[CH:6]3[CH2:19][O:20][CH2:21][CH2:22][N:5]3[C:4]=2[N:3]=1.[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1.C(=O)(O)[O-].[Na+]>O1CCOCC1.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]>[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH:12]5[CH2:17][CH2:16][O:15][CH2:14][CH2:13]5)[C:7](=[O:18])[CH:6]5[CH2:19][O:20][CH2:21][CH2:22][N:5]5[C:4]=4[N:3]=3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 86651587HCID 86651587, compound

Product 1

HCID 68194927HCID 68194927, compoundYield 23%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a microwave reaction vial were added 2-chloro-5-(tetrahydro-2H-pyran-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x55, 0.040 g, 0.123 mmol), 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.041 g, 0.135 mmol), and PdCl2(dppf) (0.018 g, 0.025 mmol) in saturated aq sodium bicarbonate (0.3 mL, 0.123 mmol) and dioxane (1.232 mL). The resulting suspension was heated by microwave irradiation at 100° C. for 1 hour, then filtered, and purified by preparatory HPLC using a 20-30% CH3CN gradient in H2O (with 0.05% TFA). The fractions were combined, concentrated in vacuo, and lyophilized to give the title compound as a white solid (13 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.45-0.62 (m, 2 H), 0.71-0.86 (m, 2 H), 1.66-1.82 (m, 2 H), 2.55-2.84 (m, 3 H), 3.17-3.40 (m, 2 H), 3.46-3.78 (m, 4 H), 4.07 (td, J=12.19, 4.17 Hz, 3 H), 4.30-4.46 (m, 2 H), 4.55 (dd, J=10.61, 3.79 Hz, 1 H), 4.96 (dd, J=13.64, 1.77 Hz, 2 H), 7.67 (d, J=8.84 Hz, 2 H), 8.01-8.26 (m, 3 H); ESI-MS m/z [M+H]+ calc'd for C24H28N6O4, 465.2; found 465.4.

Workup

  1. customTo a microwave reaction
  2. filtrationfiltered
  3. custompurified by preparatory HPLC
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7dffa4f75c4e4244b9cc2d381bc98185
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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