N,N-Dimethylglycine hydrochloride → HCID 11623424, compound

HRID 1430350Notes

Reaction equation

HRID 1430350 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([N+:15]([O-])=O)=[CH:10][CH:9]=2)=[O:5])[CH3:2].CCN=C=NCCCN(C)C.Cl.Cl.[CH3:31][N:32]([CH3:37])[CH2:33][C:34](O)=[O:35].C([O-])(O)=O.[Na+]>CCOC(C)=O.O.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([NH:15][C:34](=[O:35])[CH2:33][N:32]([CH3:37])[CH3:31])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 75605N,N-Dimethylglycine hydrochlorideHCID 280312Ethyl 5-nitro-1H-indole-2-carboxylateHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 11623424HCID 11623424, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5-nitro-1H-indole-2-carboxylic acid ethyl ester (28) (750 mg, 3.20 mmol) in EtOAc (125 mL) was hydrogenated over Pd/C (10%, 300 mg) at 60 psi H2 for 5 h at room temperature. Then, the solid was removed by filtration through Celite, which was washed thoroughly with CH2Cl2 (400 mL) and MeOH (400 mL), and the filtrate was concentrated in vacuo. The residue was dissolved in DMF (30 mL) and the solution was cooled to 0° C. EDC.HCl (1.84 g, 9.60 mmol) and N,N-dimethylglycine hydrochloride (670 mg, 4.80 mmol) were added and the reaction mixture was allowed to warm to room temperature. After stirring for 21 h at this temperature, the solution was diluted with EtOAc (100 mL) and water (100 mL). The mixture was adjusted to pH 9 with a saturated aqueous solution of NaHCO3 and extracted with EtOAc (4×150 mL). The combined organic fractions were washed with water (4×200 mL) and brine (300 mL), dried (MgSO4), and the solvent was removed in vacuo. Purification by column chromatography (CH2Cl2/MeOH, 10:1) gave 29 (626 mg, 68% overall yield) as a pale brown solid. 1H NMR (200 MHz, CDCl3): δ=1.42 (t, J=7.1 Hz, 3 H, OCH2CH3), 2.40 (s, 6 H, NMe2), 3.11 (s, 2 H, 1′-H2), 4.41 (q, J=7.1 Hz, 2 H, OCH2CH3), 7.18 (d, J=1.8 Hz, 1 H, 3-H), 7.36 (d, J=8.8 Hz, 1 H, 7-H), 7.43 (dd, J=8.8, 1.8 Hz, 1 H, 6-H), 8.04 (sbr, 1 H, 4-H), 9.04 (sbr, 1 H, NH), 9.13 (sbr, 1 H, NH) ppm; 13C NMR (50.3 MHz, CDCl3): δ=14.3 (OCH2CH3), 46.0 (NMe2), 61.0 (OCH2CH3), 63.6 (C-1′), 108.5 (C-3), 112.2, 112.8 (C-4, C-7), 119.2 (C-6), 127.5, 128.2 (C-2, C-3a), 131.1 (C-5), 134.1 (C-7a), 162.0 (NHCO), 168.6 (CO2Et) ppm; MS (70 eV, EI): m/z (%)=289 (25) [M]+, 58 (100) [CH2NMe2]+; C15H19N3O3 (289.33): calcd. 289.1426, found 289.1426.

Workup

  1. customThen, the solid was removed by filtration through Celite, which
  2. washwas washed thoroughly with CH2Cl2 (400 mL) and MeOH (400 mL)
  3. concentrationthe filtrate was concentrated in vacuo
  4. dissolutionThe residue was dissolved in DMF (30 mL)
  5. temperatureto warm to room temperature
  6. extractionextracted with EtOAc (4×150 mL)
  7. washThe combined organic fractions were washed with water (4×200 mL) and brine (300 mL)
  8. dry with materialdried (MgSO4)
  9. customthe solvent was removed in vacuo
  10. customPurification by column chromatography (CH2Cl2/MeOH, 10:1)

Sources & evidence

ORD record
ord-bd5c58f7739c48f1a642663f2b5908d6
Source dataset
uspto-grants-2015_01
Patent number
US08940784B2

Reaction notes

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