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 1764798Notes

Reaction equation

HRID 1764798 reaction equation
[CH2:1]1[NH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:2]1=[O:3].O=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.N1C2C(=CC=CC=2)C=C1.[BH3-]C#N.[Na+].[OH-].[Na+]>C(O)(C(F)(F)F)=O.O>[O:3]=[C:2]1[CH2:1][N:11]2[C@H:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][C@H:14]3[C:9]3[C:10]2=[C:5]([CH:6]=[CH:7][CH:8]=3)[NH:4]1

Participants

8

Reactant 5

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

Product 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-carboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

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′,40′: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]+

Workup

  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

Sources & evidence

ORD record
ord-c08afe8f8f6144f8a31710c0f22c1b91
Source dataset
uspto-grants-2007_06
Patent number
USRE039680E1

Reaction notes

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