Water → HCID 44512092, compound

HRID 2045995Notes

Reaction equation

HRID 2045995 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.C([O:32][C:33]1[CH:38]=[N:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].O>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>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:36]3[N:37]=[CH:38][C:33](=[O:32])[NH:34][CH:35]=3)=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-oneHCID 45785730HCID 45785730, compound

Product 1

HCID 44512092HCID 44512092, compoundYield 55.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A microwave vial, equipped with a flea stir bar, was charged with (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (22 mg, 0.051 mmol), 2-tert-butoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine (21 mg, 0.076 mmol), Cs2CO3 (33 mg, 0.10 mmol), water (0.1 mL) and dioxane (1 mL). The mixture was sparged with N2 for 5 min and PdCl2(dppf) (4 mg, 0.005 mmol) was added. The mixture was sparged with N2 for 5 min and heated at 110° C. for 40 min in the microwave. The reaction mixture was filtered and the filtrate was purified by prep HPLC under acidic conditions, which led to loss of the t-butyl group, to afford the title compound (12.6 mg, 55%) as an oil. LC-MS Method 1 tR=1.27 min, m/z=448, 390; 1H NMR (CD3OD) 0.96 (s, 3H), 1.26 (s, 3H), 1.56 (d, 3H), 2.17 (s, 2H), 2.22 (m, 1H), 2.47 (m, 2H), 3.02 (m, 1H), 5.56 (q, 1H), 7.00 (d, 2H), 7.20-7.30 (5H), 7.58 (d, 2H), 7.77 (s, 1H), 8.14 (s, 1H).

Workup

  1. customA microwave vial, equipped with a flea
  2. customThe mixture was sparged with N2 for 5 min
  3. customThe mixture was sparged with N2 for 5 min
  4. filtrationThe reaction mixture was filtered
  5. customthe filtrate was purified by prep HPLC under acidic conditions, which

Sources & evidence

ORD record
ord-66dc06c47a6541a887f3f49baa9586b1
Source dataset
uspto-grants-2013_11
Patent number
US08592410B2

Reaction notes

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