Water → (R)-methyl 2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)-4-methylbenzoate

HRID 2169582Notes

Reaction equation

HRID 2169582 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH2:12][N:13]2[CH2:22][C@@H:21]3[CH2:23][O:24][CH2:25][CH2:26][N:20]3[C:19]3[N:18]=[C:17]([Cl:27])[N:16]=[CH:15][C:14]2=3)[CH:3]=1.[C:28]([O-])([O-])=O.[K+].[K+].CB1OB(C)OB(C)O1.O>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]>[Cl:27][C:17]1[N:16]=[CH:15][C:14]2[N:13]([CH2:12][C:4]3[CH:3]=[C:2]([CH3:28])[CH:11]=[CH:10][C:5]=3[C:6]([O:8][CH3:9])=[O:7])[CH2:22][C@@H:21]3[CH2:23][O:24][CH2:25][CH2:26][N:20]3[C:19]=2[N:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86670124(R)-methyl 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoate

Product 1

HCID 86670125(R)-methyl 2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)-4-methylbenzoateYield 73%

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

(R)-methyl 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoate (PREPARATION x56, 164 mg, 0.361 mmol), K2CO3 (100 mg, 0.723 mmol), PdCl2(dppf) (13.22 mg, 0.018 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (0.060 mL, 0.434 mmol) were dissolved in dioxane (2 mL) and water (0.4 mL) to give an orange suspension. The reaction mixture was heated to 100° C. and allowed to stir overnight, then quenched with aqueous saturated NH4Cl. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was then 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 foam (102 mg, 73%). ESI-MS m/z [M+H]+ calc'd for C19H21ClN4O3, 389.14; found 389.2.

Workup

  1. customquenched with aqueous saturated NH4Cl
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with aqueous saturated NH4Cl (3×15 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washeluted
  8. customThe product was collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f6d5e8df5da74cf3b9a796c521a60ef1
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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