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

HRID 2169571Notes

Reaction equation

HRID 2169571 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)[C:7](=[O:23])[CH:6]3[CH2:24][O:25][CH2:26][CH2:27][N:5]3[C:4]=2[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH:41]=[CH:40][N:39]=[C:38]3[N:42]([S:45]([C:48]4[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=4)(=[O:47])=[O:46])[CH:43]=[CH:44][C:37]=23)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]>[CH3:22][S:19]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:8]2[C:7](=[O:23])[CH:6]3[CH2:24][O:25][CH2:26][CH2:27][N:5]3[C:4]3[N:3]=[C:2]([C:36]4[CH:41]=[CH:40][N:39]=[C:38]5[N:42]([S:45]([C:48]6[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=6)(=[O:46])=[O:47])[CH:43]=[CH:44][C:37]=45)[N:11]=[CH:10][C:9]2=3)=[CH:14][CH:15]=1)(=[O:21])=[O:20]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 497589261-Tosyl-1H-pyrrolo(2,3-B)pyridine-4-boronic acid pinacol esterHCID 86670113HCID 86670113, compound

Product 1

HCID 681946405-(4-(methylsulfonyl)benzyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-oneYield 52%

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

2-Chloro-5-(4-(methylsulfonyl)benzyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x38, 250 mg, 0.611 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (487 mg, 1.223 mmol), and PdCl2(dppf) (35.8 mg, 0.049 mmol) were suspended in dioxane (2.5 mL) and aqueous saturated NaHCO3 (0.5 mL). The reaction mixture was heated in a microwave at 100° C. on high absorbance for 1 hour and was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×2 mL) and brine (3×2 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (4 g) and eluted using an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow foam (205 mg, 52%). ESI-MS m/z [M+H]+ calc'd for C31H28N6O6S2, 645.15; found 645.5.

Workup

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

Sources & evidence

ORD record
ord-10ced951d69a44e09744a98c11287c61
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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