Sodium Bicarbonate → 5-benzyl-2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

HRID 2169640Notes

Reaction equation

HRID 2169640 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[CH:16]2[CH2:19][O:20][CH2:21][CH2:22][N:15]2[C:14]2[N:13]=[C:12](Cl)[N:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:40]=[CH:39][CH:38]=[C:37]3[C:33]=2[CH:34]=[CH:35][NH:36]3)O1.C([O-])(O)=O.[Na+]>O1CCOCC1.C(OCC)(=O)C.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]>[CH2:1]([N:8]1[C:17](=[O:18])[CH:16]2[CH2:19][O:20][CH2:21][CH2:22][N:15]2[C:14]2[N:13]=[C:12]([C:32]3[CH:40]=[CH:39][CH:38]=[C:37]4[C:33]=3[CH:34]=[CH:35][NH:36]4)[N:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 866701145-benzyl-2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 681951745-benzyl-2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-oneYield 32.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Benzyl-2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x39, 200 mg, 0.605 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (294 mg, 1.209 mmol), and PdCl2(dppf) (22.12 mg, 0.030 mmol) was suspended in dioxane (3 mL) and aqueous saturated NaHCO3 (0.6 mL). The resulting brown suspension was heated to 100° C. for 18 hours, then diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×5 mL) and brine (3×5 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give crude product, which was loaded onto an ISCO® silica gel cartridge (12 g) and eluted using an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white solid (80 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ 3.06-3.19 (m, 1 H), 3.58-3.74 (m, 2 H), 4.01-4.12 (m, 1 H), 4.25-4.34 (m, 1 H), 4.49-4.63 (m, 2 H), 5.12-5.31 (m, 2 H), 7.11-7.18 (m, 1 H), 7.24-7.40 (m, 6 H), 7.40-7.44 (m, 1 H), 7.46-7.51 (m, 1 H), 7.99-8.03 (m, 1 H), 8.04-8.07 (m, 1 H), 11.20-11.26 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C24H21N5O2, 412.17; found 412.4.

Workup

  1. washwashed with aqueous saturated NH4Cl (3×5 mL) and brine (3×5 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give crude product, which
  6. washeluted
  7. customThe product was collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cb74118999f74254855ca8c8bc1d4b6c
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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