Methylamine → HCID 57474472, compound

HRID 2223819Notes

Reaction equation

HRID 2223819 reaction equation
CN[CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=2)[CH:8]=[CH:7]1.CN.N1(CCCN2C3C(=CC=C(NC(C4SC=CC=4)=N)C=3)C=C2)CCOCC1.I.[ClH:47].N1(CCCN2C3C(=CC=C(NC(C4SC=CC=4)=N)C=3)C=C2)CCOCC1.Cl.Cl.CNCCCN1C2C(=CC=C(NC(C3SC=CC=3)=N)C=2)C=C1>>[Cl:47][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=2)[CH:8]=[CH:7]1

Participants

7

Reactant 6

HCID 6329MethylamineHCID 24841Hydrogen iodideHCID 59715776HCID 59715776, compoundHCID 178479300HCID 178479300, compoundHCID 178483701HCID 178483701, compoundHCID 178511927HCID 178511927, compound

Product 1

HCID 57474472HCID 57474472, compound

Procedure

Procedure described under Example 40. (Yield: 796.6 mg, greater than 100%) Preparation of N-methyl-3-(6-nitro-1H-indol-1-yl)propan-1-amine (158): Reaction performed as described in Example 40, using methylamine as nucleophile. The product was purified using silica gel column chromatography (2.5-5% 2M ammonia in methanol, 97.5-95% dichloromethane). Yield: 91.7 mg of compound 158 as a dark yellow oil (94.1%). 1H-NMR (CDCl3) δ 8.40-8.39 (d, J=1.8 Hz, 1H), 8.02-7.99 (dd, J=2.1, 9 Hz, 1H), 7.66-7.63 (d, J=8.7 Hz, 1H), 7.42-7.41 (d, J=3 Hz, 1H), 6.60-6.59 (d, J=3.3 Hz, 1H), 4.36-4.31 (t, J=6.9 Hz, 2H), 2.59-2.54 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.07-1.98 (quintet, J=6.7 Hz, 2H) Preparation of N-(1-(3-(methylamino)propyl)-1H-indol-6-yl)thiophene-2-carboximidamide dihydrochloride (159): Reaction performed as described in Example 40, compound 150. Following isolation of the HI salt by precipitation (121.9 mg), the salt was dissolved in ethanol. Treated amberlite resin (3.00 g) was added to the solution, and the mixture stirred at room temperature for 35 minutes. The reaction was diluted with ethyl acetate (15 mL) and filtered. The filtrate was concentrated to afford a yellow oil. The material was absorbed onto silica gel and purified by silica gel column chromatography (5-10% 2M ammonia in methanol, 95-90% dichloromethane). Reaction converted to hydrochloride salt using procedure described in Example 40 for compound 151. Yield: 87.2 mg of compound 159 as a yellow-orange solid. 1H-NMR (DMSO-d6) δ 7.74-7.73 (d, J=3.6 Hz, 1H), 7.61-7.59 (d, J=4.5, 1H), 7.46-7.43 (d, J=8.1 Hz, 1H), 7.21-7.20 (d, J=3 Hz, 1H), 7.11-7.09 (t, J=4.8 Hz, 1H), 6.92 (s, 1H0), 6.60-6.57 (dd, J=1.2, 8.4 Hz, 1H), 6.34-6.33 (d, J=3 Hz, 2H), 4.17-4.12 (t, J=6.9 Hz, 2H), 2.46-2.41 (t, J=6.6 Hz, 2H), 2.25 (s, 3H), 1.87-1.83 (quintet, J=6.7 Hz, 2H). ESI-MS m/z (%): 327 (+, 100).

Workup

  1. customReaction
  2. customThe product was purified
  3. custom1H-NMR (CDCl3) δ 8.40-8.39 (d, J=1.8 Hz, 1H), 8.02-7.99 (dd, J=2.1, 9 Hz, 1H), 7.66-7.63 (d, J=8.7 Hz, 1H), 7.42-7.41 (d, J=3 Hz, 1H), 6.60-6.59 (d, J=3.3 Hz, 1H), 4.36-4.31 (t, J=6.9 Hz, 2H), 2.59-2.54 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.07-1.98 (quintet, J=6.7 Hz, 2H) Preparation of N-(1-(3-(methylamino)propyl)-1H-indol-6-yl)thiophene-2-carboximidamide dihydrochloride (159)
  4. customReaction
  5. customby precipitation (121.9 mg)
  6. dissolutionthe salt was dissolved in ethanol
  7. additionTreated amberlite resin (3.00 g)
  8. additionwas added to the solution
  9. additionThe reaction was diluted with ethyl acetate (15 mL)
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. customto afford a yellow oil
  13. customThe material was absorbed onto silica gel
  14. custompurified by silica gel column chromatography (5-10% 2M ammonia in methanol, 95-90% dichloromethane)
  15. customReaction

Sources & evidence

ORD record
ord-b1bd2964bcbd4dd0ab07d35a0c7fa863
Source dataset
uspto-grants-2008_05
Patent number
US07375219B2

Reaction notes

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