Sodium Chloride → HCID 51352112, compound

HRID 1696011Notes

Reaction equation

HRID 1696011 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][CH:13]3[CH2:15][CH2:14]3)[C:7](=[O:16])[C@:6]3([CH3:22])[C@H:17]([CH3:21])[O:18][CH2:19][CH2:20][N:5]3[C:4]=2[N:3]=1.[CH3:23][NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1)=[O:26].C([O-])(O)=O.[Na+].[Na+].[Cl-]>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].O1CCOCC1>[CH:13]1([CH2:12][N:8]2[C:7](=[O:16])[C@:6]3([CH3:22])[C@H:17]([CH3:21])[O:18][CH2:19][CH2:20][N:5]3[C:4]3[N:3]=[C:2]([C:31]4[CH:30]=[CH:29][C:28]([NH:27][C:25]([NH:24][CH3:23])=[O:26])=[CH:33][CH:32]=4)[N:11]=[CH:10][C:9]2=3)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651577HCID 86651577, compound

Product 1

HCID 51352112HCID 51352112, compoundYield 5.3%

Reagents, catalysts & solvents 2

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

Procedure

A microwave vial equipped with a magnetic stirrer was added crude (6aS,7S)-2-chloro-5-(cyclopropylmethyl)-6a,7-dimethyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (98 mg, 0.304 mmol), 1,4-dioxane (1.5 ml), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (126 mg, 0.455 mmol), saturated NaHCO3 (0.500 mL), and PdCl2(dppf) (11.11 mg, 0.015 mmol). The reaction was irradiated in the microwave at 100° C. for 40 minutes. The reaction solution was poured into saturated NaCl and extracted with ethyl acetate three times. The organic layers were collected, dried over Na2SO4, filtered and concentrated in-vacuo to give a brown residue. The residue was purified by preparative HPLC (eluting with 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to afford the title compound (6.8 mg, 0.016 mmol, 5.13% yield) as a light brown solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.46 (m, 2 H) 0.60 (m, 2 H) 1.20-1.25 (m, 1 H) 1.41 (d, J=6.6 Hz, 3 H) 1.92 (s, 3 H) 2.81 (s, 3 H) 3.53-3.67 (m, 1 H) 3.79-3.87 (m, 1 H) 3.91 (d, J=7.0 Hz, 2 H) 3.99-4.11 (m, 1 H) 4.27 (d, J=6.6 Hz, 1H) 4.87-5.00 (m, 1 H) 7.65 (d, J=8.8 Hz, 2 H) 7.97 (s, 1 H) 8.11 (d, J=8.8 Hz, 2 H). MS [M+H] found 437.

Workup

  1. customA microwave vial equipped with a magnetic stirrer
  2. customThe reaction was irradiated in the microwave at 100° C. for 40 minutes
  3. extractionextracted with ethyl acetate three times
  4. customThe organic layers were collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in-vacuo
  8. customto give a brown residue
  9. customThe residue was purified by preparative HPLC (
  10. washeluting with 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-24f9d7a727ec42a2b6408bef9c25d266
Source dataset
uspto-grants-2012_04
Patent number
US08163755B2

Reaction notes

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