Indole → ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

HRID 350780

반응식

HRID 350780 반응식
[CH2:1]([O:3][C:4]([N:6]1[CH2:22][CH2:21][C:9]2[N:10]3[C:19]4[C:18]([C:8]=2[CH2:7]1)=[CH:17][CH:16]=[CH:15][C:14]=4[NH:13][C:12](=[O:20])[CH2:11]3)=[O:5])[CH3:2].C1NC2C(=CC=CC=2)NC1=O.O=C1CCN(C(OCC)=O)CC1.N1C2C(=CC=CC=2)C=C1.[BH3-]C#N.[Na+].[OH-].[Na+]>C(O)(C(F)(F)F)=O.O>[O:20]=[C:12]1[CH2:11][N:10]2[C@H:9]3[CH2:21][CH2:22][N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][C@H:8]3[C:18]3[C:19]2=[C:14]([CH:15]=[CH:16][CH:17]=3)[NH:13]1

참가 물질

9

반응물 6

HCID 798IndoleHCID 14798Sodium HydroxideHCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 1859492(1H)-Quinoxalinone, 3,4-dihydro-HCID 5003444Sodium cyanoborohydrideHCID 22036738Lumat-004

생성물 1

HCID 20578971ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate수율 77%

시약·촉매·용매 2

HCID 962Water용매HCID 6422Trifluoroacetic acid용매

반응 조건

온도
0 °C

실험 절차

The procedure described in Example 4, Steps E through G, was utilized to prepare ethyl-2-oxo-2,3,9,10-tetrahydro-1H-pyrido[3′,4′:4,5]-pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate from the corresponding amine, 1,3,4-trihydroquinoxalin-2-one, and ethyl 4-oxopiperidinecarboxylate. This indole (5.74 g, 19.2 mmol) was dissolved in TFA (100 mL). The reaction was cooled to 0° C. NaCNBH3 (3.96 g, 63.0 mmol) was added in small portions over 30 min, keeping the temperature less than 5° C. The reaction was stirred at r.t. for 4 hr. Ice was added to the reaction flask, and the reaction was basified with 50% NaOH until pH=12. Water (80 mL) was added to dissolve the precipitate. The reaction was extracted with CHCl3 (3×200 mL). The combined organic layers were washed with brine, dried, and concentrated to afford ethyl (6bR,10aS)-2-oxo-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate (4.41 g, 77%). 1H NMR (CDCl3, 300 MHz) δ 8.45 (bs, 1H), 6.86 (d, J=7.4 Hz, 1H), 6.74 (dd, J=7.7 Hz, 7.7 Hz, 1H), 6.63 (d, J=7.3 Hz, 1H), 4.15 (q, J=7.0 Hz, 2H), 3.89–3.993 (m, 2H), 3.41–3.47 (m, 2H), 3.33–3.41 (m, 2H), 3.12–3.31 (m, 1H), 2.69–2.75 (m, 2H), 1.90–1.92 (m, 2H), 1.28 (t, J=7.3 Hz, 3H) ppm. MS-APcI: 302 [MH]+

후처리

  1. customthe temperature less than 5° C
  2. additionIce was added to the reaction flask
  3. dissolutionto dissolve the precipitate
  4. extractionThe reaction was extracted with CHCl3 (3×200 mL)
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-b3df29d4e97448eeb944f45fc037ce6c
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07183282B2

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