Sodium Carbonate → (S)-1-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-one

HRID 219618Notes

Reaction equation

HRID 219618 reaction equation
[CH3:1][C:2](=[CH2:35])[CH2:3][C@:4]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:10][CH2:9][CH2:8][N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[C:6](=[O:28])[NH:5]1.Br[C:37]1[CH:38]=[CH:39][C:40](=[O:44])[N:41]([CH3:43])[CH:42]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH3:43][N:41]1[C:40](=[O:44])[CH:39]=[CH:38][C:37]([C:16]2[CH:15]=[CH:14][C:13]([C@@H:11]([N:7]3[CH2:8][CH2:9][CH2:10][C@:4]([CH2:3][C:2]([CH3:1])=[CH2:35])([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[NH:5][C:6]3=[O:28])[CH3:12])=[CH:18][CH:17]=2)=[CH:42]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 130240275-Bromo-1-methylpyridin-2(1H)-oneHCID 59190370(S)-4-(2-methylallyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-diazepan-2-one

Product 1

HCID 59190381(S)-1-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-oneYield 44%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

(S)-4-(2-methylallyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-diazepan-2-one (38 mg, 0.08 mmol), 5-bromo-1-methylpyridin-2(1H)-one (23 mg, 1.5 equiv.), Pd(PPh3)2Cl2 (2 mg, cat. amount), 2M aq Na2CO3 (500 μL, excess), and 1,4-Dioxane (4 mL) were mixed. The mixture was evacuated and refilled with nitrogen gas (3×), before being heated to 90° C. overnight. After being cooled down, the mixture was concentrated, acidified with 5% aq HCl and purified by prep HPLC to afford (S)-1-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-one (16 mg, 44%). LC-MS Method 1 tR=1.76 min., m/z 456 (M+1); 1H NMR (CD3OD) δ 7.90 (s, 1H), 7.80 (dd, 1H), 7.47 (d, 2H), 7.39 (t, 2H), 7.30 (d, 3H), 6.96 (d, 2H), 6.61 (d, 1H), 5.32 (q, 1H), 5.02 (d, 1H), 3.61 (s, 3H), 2.59-2.45 (m, 2H), 1.49 (d, 3H), 1.15 (s, 3H).

Workup

  1. customThe mixture was evacuated
  2. additionrefilled with nitrogen gas (3×)
  3. temperatureAfter being cooled down
  4. concentrationthe mixture was concentrated
  5. custompurified by prep HPLC

Sources & evidence

ORD record
ord-d321845960554c3c92d4aad677deafe5
Source dataset
uspto-grants-2012_06
Patent number
US08202857B2

Reaction notes

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