Triethylamine → N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide

HRID 1886737Notes

Reaction equation

HRID 1886737 reaction equation
[CH2:1]([O:3][CH2:4][N:5]1[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]([C:14]([OH:16])=O)[C:8]=2[CH:7]=[CH:6]1)[CH3:2].[CH:17]1([NH2:20])[CH2:19][CH2:18]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C1COCC1>[CH:17]1([NH:20][C:14]([C:9]2[C:8]3[CH:7]=[CH:6][N:5]([CH2:4][O:3][CH2:1][CH3:2])[C:13]=3[CH:12]=[CH:11][CH:10]=2)=[O:16])[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 69828CyclopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674641781-(ethoxymethyl)-1H-indole-4-carboxylic acid

Product 1

HCID 67466461N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamideYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(ethoxymethyl)-1H-indole-4-carboxylic acid (123 g, 0.56 mol) in THF (1.5 L) is added cyclopropylamine (58 mL, 0.84 mol) and triethylamine (TEA, 167 mL, 1.12 mol), followed by O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (240 g, 0.62 mol) at 0° C. The reaction mixture is stirred at ambient temperature overnight. The volatiles are removed in vacuo. The residue is stirred in EA (1.5 L) and HCl (0.5%, 1 L) for 10 minutes. The organic layer is separated, washed with aqueous saturated sodium chloride (3×100 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue is purified by chromatography on silica gel to give the title compound (110 g, 77%). MS (m/z): 259 (M+H)+.

Workup

  1. customThe volatiles are removed in vacuo
  2. stirringThe residue is stirred in EA (1.5 L)
  3. waitHCl (0.5%, 1 L) for 10 minutes
  4. customThe organic layer is separated
  5. washwashed with aqueous saturated sodium chloride (3×100 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by chromatography on silica gel

Sources & evidence

ORD record
ord-98b1b6cd4ef04de5ab8cd2984f759fff
Source dataset
uspto-grants-2013_08
Patent number
US08501166B2

Reaction notes

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