Triethylamine → 6-methoxy-1-methyl-7-[(2(S)-phenyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one

HRID 1244059

반응식

HRID 1244059 반응식
[CH3:1][O:2][C:3]1[C:12]([CH:13]=O)=[CH:11][C:10]2[N:9]([CH3:15])[C:8](=[O:16])[CH2:7][CH2:6][C:5]=2[N:4]=1.[C:17]1([C@H:23]2[C@@H:28]([NH2:29])[CH2:27][CH2:26][CH2:25][NH:24]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:29][C@H:28]1[CH2:27][CH2:26][CH2:25][NH:24][C@H:23]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[N:9]([CH3:15])[C:8](=[O:16])[CH2:7][CH2:6]2

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 9812908(2S,3S)-2-phenylpiperidin-3-amineHCID 219317642-Methoxy-5-methyl-6-oxo-5,6,7,8-tetrahydro-[1,5]naphthyridine-3-carbaldehyde

생성물 1

HCID 210693296-methoxy-1-methyl-7-[(2(S)-phenyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one수율 71.7%

시약·촉매·용매 1

HCID 63651,1-Dichloroethane용매

실험 절차

The 2-methoxy-5-methyl-6-oxo-5,6,7,8-tetrahydro-[1,5]naphthyridine-3-carbaldehyde prepared in step 5 (0.35 g; 1.4 mmol) was dissolved in 20 ml of dichloroethane. To this was added 250 mg (1.1 mmol) of 2-(S)-phenyl-piperidin-3(S)-ylamine and 0.4 ml (2.8 mmol) of triethylamine, and the mixture was stirred for 60 minutes at room temperature. To this mixture was added 0.7 g (3.3 mmol) of sodium triacetoxyborohydride, and the reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with water and stirred at room temperature for 30 minutes. The pH of the mixture was adjusted to 8.5 with Na2CO3. The organic layer was separated from the water layer. An additional 20 ml of water was added to the organic layer. The pH of the mixture was adjusted to 2 with 1N HCl and extracted with ethyl acetate. The pH of the water layer was adjusted to 7.5 with sodium bicarbonate and extracted with ethyl acetate. The pH=7.5 ethyl acetate extracts were combined, dried (Na2SO4), and evaporated to yield 300 mg of 6-methoxy-1-methyl-7-[(2(S)-phenyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one. 1H NMR (CDCl3) δ 7.2–7.4 (m, 5H), 6.85 (s, 1H), 3.90 (s, 1H), 3.85 (s, 3H), 3.60,3.38 (d,d 2H), 3.30 (d, 1H), 3.10 (s, 3H), 3.0 (s, 1H), 2.90 (m, 2H), 2.80 (m, 2H), 2.66 (m, 2H), 2.0–2.2 (m, 3H), 1.9 (m, 1H), 1.6 (m, 1H), 1.45 (m, 1H). Mass spectrum: m/e=381.1 (p+1). TLC: Rf=0.5; (5:1 chloroform/methanol).

후처리

  1. stirringthe reaction mixture was stirred at room temperature for 18 hours
  2. customThe reaction was quenched with water
  3. stirringstirred at room temperature for 30 minutes
  4. customThe organic layer was separated from the water layer
  5. additionAn additional 20 ml of water was added to the organic layer
  6. extractionextracted with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. dry with materialdried (Na2SO4)
  9. customevaporated

출처 및 근거

ORD 기록
ord-2f022352ddf64c479f59e3fa53b83a3d
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07119207B2

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