Sodium Bicarbonate → HCID 68194828, compound

HRID 2169637Notes

Reaction equation

HRID 2169637 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH3:13])[C:7](=[O:21])[CH:6]3[CH2:22][O:23][CH2:24][CH2:25][N:5]3[C:4]=2[N:3]=1.[CH3:26][NH:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1)=[O:29].C([O-])(O)=O.[Na+]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([C@@H:12]([N:8]2[C:7](=[O:21])[CH:6]3[CH2:22][O:23][CH2:24][CH2:25][N:5]3[C:4]3[N:3]=[C:2]([C:34]4[CH:33]=[CH:32][C:31]([NH:30][C:28]([NH:27][CH3:26])=[O:29])=[CH:36][CH:35]=4)[N:11]=[CH:10][C:9]2=3)[CH3:13])=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86762575HCID 86762575, compound

Product 1

HCID 68194828HCID 68194828, compoundYield 16.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a 2 mL microwave vial were added 2-chloro-5-((S)-1-(4-chlorophenyl)ethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x51, 100 mg, 0.264 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (146 mg, 0.527 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (10.85 mg, 0.013 mmol). After the vial was sealed, dioxane (1.5 mL) and aqueous saturated NaHCO3 (0.38 mL) were added, and the mixture was degassed by bubbling nitrogen through a syringe needle for 10 minutes. The mixture was then heated in a microwave to 120° C. for 30 minutes. The reaction mixture was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by normal phase column chromatography (SiO2, 50-100% EtOAc/hexanes in 20 minutes) to give the title compound (single diastereomer, 21 mg, 16%). 1H NMR (400 MHz, DMSO-d6) δ 1.75 (d, J=7.1 Hz, 1H), 1.83 (d, J=7.1 Hz, 3H), 2.65 (d, J=4.5 Hz, 3H), 2.95-3.07 (m, 1H), 3.55-3.73 (m, 2H), 4.02 (dd, J=11.6, 3.0 Hz, 1H), 4.25 (dd, J=11.2, 3.7 Hz, 1H), 4.40 (dd, J=10.6, 3.8 Hz, 1H), 4.45-4.54 (m, 1H), 6.02-6.09 (m, 1H), 6.14 (d, J=7.1 Hz, 1H), 7.33-7.50 (m, 7H), 7.60 (s, 1H), 7.76 (s, 1H), 8.07-8.16 (m, 2H), 8.70 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C25H25ClN6O3, 493.17; found 493.4.

Workup

  1. customAfter the vial was sealed
  2. customthe mixture was degassed
  3. customby bubbling nitrogen through a syringe needle for 10 minutes
  4. customThe reaction mixture was partitioned between brine and ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by normal phase column chromatography (SiO2, 50-100% EtOAc/hexanes in 20 minutes)

Sources & evidence

ORD record
ord-3739fdf532b240dda92ad83b364e67ac
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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