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

HRID 219620Notes

Reaction equation

HRID 219620 reaction equation
[OH:1][C:2]([CH3:36])([CH3:35])[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:38]1[CH:43]=[CH:42][N:41]([CH3:44])[C:40](=[O:45])[CH:39]=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>[OH:1][C:2]([CH3:35])([CH3:36])[CH2:3][C@:4]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:10][CH2:9][CH2:8][N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:38]3[CH:43]=[CH:42][N:41]([CH3:44])[C:40](=[O:45])[CH:39]=3)=[CH:17][CH:18]=2)[CH3:12])[C:6](=[O:28])[NH:5]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 221323964-Bromo-1-methylpyridin-2(1H)-oneHCID 59190387(S)-4-(2-hydroxy-2-methylpropyl)-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 59190399(S)-4-(2-hydroxy-2-methylpropyl)-1-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-4-phenyl-1,3-diazepan-2-oneYield 39.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

(S)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-diazepan-2-one (10 mg, 0.02 mmol), 4-bromo-1-methylpyridin-2(1H)-one (7.6 mg, 2 equiv.), Pd(PPh3)2Cl2 (1 mg, cat. amount), 2M aq Na2CO3 solution (200 μL, excess), and 1,4-dioxane (2 mL) were mixed. The mixture was evacuated and refilled with Nitrogen gas 3×, before being heated to 130° C. in the microwave oven for 2 h. After being cooled down, the mixture was concentrated, acidified with 5% aq HCl and purified by prep HPLC to afford (S)-4-(2-hydroxy-2-methylpropyl)-1-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-4-phenyl-1,3-diazepan-2-one (3.7 mg, 38%). LC-MS Method 1 tR=1.53 min., m/z 474 (M+1); H1 NMR (CD3OD) δ 7.63 (d, 1H), 7.51 (d, 2H), 7.43 (d, 2H), 7.32 (t, 2H), 7.22 (t, 1H), 7.14 (d, 2H), 6.74-6.59 (m, 2H), 5.42 (q, 1H), 3.55 (s, 3H), 2.89 (m, 1H), 2.71 (m, 1H), 2.34 (d, 1H), 1.49 (d, 3H), 1.12 (s, 3H), 0.54 (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-ae0cd092d6af4f9c99e7aabc1aa3148b
Source dataset
uspto-grants-2012_06
Patent number
US08202857B2

Reaction notes

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