Sodium Bicarbonate → 6-cyclopropyl-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 406758

Reaction equation

HRID 406758 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=1.[OH:10][C:11]([CH3:42])([CH3:41])[CH2:12][CH2:13][C:14]1([CH:38]([CH3:40])[CH3:39])[O:19][C:18](=[O:20])[N:17]([C@H:21]([C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[CH3:22])[CH2:16][CH2:15]1.[CH:43]1([C:46]2([CH2:69][C:70]([OH:73])([CH3:72])[CH3:71])[O:51][C:50](=[O:52])[N:49]([C@H:53]([C:55]3[CH:60]=[CH:59][C:58]([C:61]4[CH:66]=[CH:65][N:64]([CH3:67])[C:63](=[O:68])[CH:62]=4)=[CH:57][CH:56]=3)[CH3:54])[CH2:48][CH2:47]2)[CH2:45][CH2:44]1.C([O-])(O)=O.[Na+]>COCCOC.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:10][C:11]([CH3:41])([CH3:42])[CH2:12][CH2:13][C:14]1([CH:38]([CH3:39])[CH3:40])[O:19][C:18](=[O:20])[N:17]([C@H:21]([C:23]2[CH:24]=[CH:25][C:26]([C:2]3[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=3)=[CH:27][CH:28]=2)[CH3:22])[CH2:16][CH2:15]1.[CH:43]1([C:46]2([CH2:69][C:70]([OH:73])([CH3:72])[CH3:71])[O:51][C:50](=[O:52])[N:49]([C@H:53]([C:55]3[CH:60]=[CH:59][C:58]([C:61]4[CH:66]=[CH:65][N:64]([CH3:67])[C:63](=[O:68])[CH:62]=4)=[CH:57][CH:56]=3)[CH3:54])[CH2:48][CH2:47]2)[CH2:44][CH2:45]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 596356736-cyclopropyl-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-oneHCID 596357086-(3-hydroxy-3-methylbutyl)-6-isopropyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 2

HCID 596356736-cyclopropyl-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-oneYield 65.8%HCID 667821246-(3-hydroxy-3-methylbutyl)-6-isopropyl-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of compound 4-iodo-1-methylpyridin-2(1H)-one (17 mg, 0.074 mmol) in DME (4.6 mL) was added Pd(PPh3)4 (6.7 mg, 0.007 mmol) under nitrogen. The mixture was stirred at room temperature for 1 h, and a solution of compound 6-(3-hydroxy-3-methylbutyl)-6-isopropyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one isomer 1 (17 mg, 0.037 mmol) in EtOH (2 mL) and satd aq NaHCO3 (1.5 mL) were added. The mixture was stirred at 100° C. for 2 h, quenched with water, and extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give the compound 6-(3-hydroxy-3-methylbutyl)-6-isopropyl-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one isomer 1 (10.73 mg, 65.8%). LC-MS Method 2 Method 2 tR=1.03 min, m/z=463, 441;1H NMR (CD3OD): δ 0.89 (m, 6H), 1.11 (s, 6H), 1.42 (m, 2H), 1.51(m, 3H), 1.60 (m, 2H), 1.82-2.02 (m, 2H), 2.69 (m, 1H), 3.03 (m, 1H), 3.51 (s, 3H), 5.79 (m, 3H), 6.35 (d, 1H), 6.72 (s, 1H), 7.28 (d, 1H),7.39 (d, 2H), 7.49 (m, 2H).

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at 100° C. for 2 h
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-323b27d92d0f490989a74c62ff98483e
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Linked notes

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