Diethylamine → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-((2-methoxypyridin-4-yl)ethynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

HRID 333907

반응식

HRID 333907 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([N:11]2[CH2:16][CH2:15][C@:14]([CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:13][C:12]2=[O:28])[CH3:10])=[CH:5][CH:4]=1)#[CH:2].Br[C:30]1[CH:35]=[CH:34][N:33]=[C:32]([O:36][CH3:37])[CH:31]=1.C(NCC)C>[Cu]I.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.CN(C=O)C>[OH:27][C:24]([CH3:25])([CH3:26])[CH2:23][C@@:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[O:13][C:12](=[O:28])[N:11]([C@H:9]([C:6]2[CH:5]=[CH:4][C:3]([C:1]#[C:2][C:30]3[CH:35]=[CH:34][N:33]=[C:32]([O:36][CH3:37])[CH:31]=3)=[CH:8][CH:7]=2)[CH3:10])[CH2:16][CH2:15]1

참가 물질

7

반응물 3

HCID 8021DiethylamineHCID 140623094-Bromo-2-methoxypyridineHCID 86670541(S)-3-((S)-1-(4-ethynylphenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

생성물 1

HCID 49870702(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-((2-methoxypyridin-4-yl)ethynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one수율 10.7%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
120 °C

실험 절차

A mixture of (S)-3-((S)-1-(4-ethynylphenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (10 mg, 0.027 mmol), 4-bromo-2-methoxypyridine (10 mg, 2 equiv), CuI (0.5 mg, 10% mol), Pd(PPh3)2Cl2 (1.9 mg, 10% mol), diethylamine (1 mL), dry DMF (1 mL) was degassed, refilled with nitrogen gas (3×). The mixture was then heated in the microwave for 45 min at 120° C. LC-MS found the reaction was complete. The mixture was filtered, concentrated, acidified with 5% aq HCl and purified by prep HPLC to afford (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-((2-methoxypyridin-4-yl)ethynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (1.4 mg). LC-MS Method 1 tR=1.92 min, m/z 485 (M+1); 1H NMR (CD3OD) 7.41-7.27 (m, 7H), 6.97 (m, 4H), 5.55 (q, 1H), 3.92 (s, 3H), 3.04 (m, 1H), 2.49 (m, 2H), 2.21 (m, 1H), 2.14 (s, 2H), 1.53 (d, 3H), 1.28 (t, 1H), 1.26 (s, 3H), 0.96 (s, 3H).

후처리

  1. customwas degassed
  2. additionrefilled with nitrogen gas (3×)
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. custompurified by prep HPLC

출처 및 근거

ORD 기록
ord-6cd802bca1804c829811ddd190997ff4
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883778B2

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