Tetrahydrofuran → Ethyl 2-((4-bromo-7-cyano-1H-indol-3-yl)methylamino)-3,3-diethoxypropanoate

HRID 2361440Notes

Reaction equation

HRID 2361440 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[C:7]2[C:3]=1[C:4]([CH:13]=O)=[CH:5][NH:6]2.[NH2:15][CH:16]([CH:22]([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[C:17]([O:19][CH2:20][CH3:21])=[O:18].C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CCOC(C)=O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[C:7]2[C:3]=1[C:4]([CH2:13][NH:15][CH:16]([CH:22]([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5][NH:6]2

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydride2×HCID 11790347Ethyl 2-amino-3,3-diethoxypropanoateHCID 866815304-Bromo-3-formyl-1H-indole-7-carbonitrile

Product 1

HCID 67995067Ethyl 2-((4-bromo-7-cyano-1H-indol-3-yl)methylamino)-3,3-diethoxypropanoateYield 35%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-3-formyl-1H-indole-7-carbonitrile (1.08 g, 4.34 mmol), ethyl 2-amino-3,3-diethoxypropanoate (prepared according to the procedure of U.S. Pat. No. 7,470,680; 1.780 g, 6.94 mmol), and molecular sieves (2.17 g, 2 g) in 1,2-dichloroethane (79 mL) and THF (29.6 mL) at 0° C. was treated with sodium triacetoxyborohydride (2.57 g, 12.14 mmol) and the resulting mixture was stirred at room temperature overnight. After 24 h, LCMS residual starting material, so additional sodium triacetoxyborohydride (1.38 g, 1.5 eq.) and molecular sieves (2 g) were added and stirring was continued for 4 h more. The mixture was diluted with EtOAc and filtered through a CELITE® pad and the solids were washed with EtOAc. The filtrates were diluted with EtOAc and washed with NaHCO3 (aq) and brine, dried and concentrated to afford a dark-colored oil. The residue was subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 15:85 to 100:0) to provide the desired product as a brown syrup (0.67 g, 35% yield). LCMS (M+H)+ m/z 438.2, 440.2.

Workup

  1. customprepared
  2. waitAfter 24 h
  3. additionwere added
  4. stirringstirring
  5. waitwas continued for 4 h
  6. filtrationfiltered through a CELITE® pad
  7. washthe solids were washed with EtOAc
  8. additionThe filtrates were diluted with EtOAc
  9. washwashed with NaHCO3 (aq) and brine
  10. customdried
  11. concentrationconcentrated
  12. customto afford a dark-colored oil
  13. washeluting with EtOAc-hexane (gradient from 15:85 to 100:0)

Sources & evidence

ORD record
ord-861d4374a211457bba93fa452afacade
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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