1H-Indole-1-propionic acid → HCID 10100043, compound

HRID 346801Notes

Reaction equation

HRID 346801 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][C:6]([N:15]([CH3:17])[CH3:16])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[N:36]1([CH2:45][CH2:46][C:47](O)=[O:48])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[CH:37]1>CO>[CH3:16][N:15]([CH3:17])[C:6]1([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:5][CH2:4][CH:3]([CH2:2][NH:1][C:47](=[O:48])[CH2:46][CH2:45][N:36]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=[CH:37]2)[CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 811391H-Indole-1-propionic acidHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 10100043HCID 10100043, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of the diastereoisomers of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (465 mg, 2.0 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (830 mg, 3 mmol.) was added to a solution of 3-indol-1-ylpropionic acid (383 mg, 2.0 mmol.) in abs. methanol (35 ml), and stirring was carried out for 2 d at RT. For working up, the mixture was concentrated, water (15 ml) was added to the residue, the pH was adjusted to 11 with 5M NaOH and extraction was carried out with EE (4×15 ml). The combined extracts were dried, filtered and concentrated. A mixture of the diastereoisomeric bases of the target product was obtained as the residue and was separated by flash chromatography on silica gel (70 g) and purified (eluant: 1300 ml of methanol/EE 1:1). 254 mg of the non-polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexylmethyl)-3-indol-1-ylpropionamide were obtained in the form of a viscous oil. 226 mg (0.56 mmol.) thereof were dissolved in abs. ethanol (3 ml) and added dropwise at RT, with stirring, to citric acid (108 mg, 0.56 mmol.) dissolved in hot ethanol (1 ml). After stirring for 1 h at RT, the white precipitate that had formed was filtered off with suction, washed with cold ethanol (1 ml) and with diethyl ether (3×1 ml) and dried in vacuo. 262 mg of the corresponding citrate were obtained (light-beige solid, m.p. 192–194° C.).

Workup

  1. concentrationthe mixture was concentrated
  2. additionwater (15 ml) was added to the residue
  3. extractionthe pH was adjusted to 11 with 5M NaOH and extraction
  4. customThe combined extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionA mixture of the diastereoisomeric bases of the target product
  8. customwas obtained as the residue
  9. customwas separated by flash chromatography on silica gel (70 g)
  10. custompurified (eluant: 1300 ml of methanol/EE 1:1)

Sources & evidence

ORD record
ord-69680eaaa46d4a4494777d2190c74a90
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Reaction notes

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