4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide

HRID 346794

Reaction equation

HRID 346794 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.[NH:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][C:50](O)=[O:51])=[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:50](=[O:51])[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45][C:38]2[C:39]3[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=3)[NH:36][CH:37]=2)[CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 46727896-(1H-indol-3-yl)hexanoic acidHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 98265266-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amideYield 59.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The non-polar diastereoisomer of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (232 mg, 1.0 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (415 mg, 1.5 mmol.) were added to a solution of 6-(1H-indol-3-yl)hexanoic acid (231 mg, 1.0 mmol.) in abs. methanol, and stirring was carried out for 24 h at RT. For working up, the mixture was concentrated and the residue was suspended in water (10 ml), adjusted to pH 11 with 5M NaOH and extracted with EE (4×10 ml). The combined organic extracts were washed with 1M NaOH (2×2 ml), dried, filtered and concentrated. The residue was purified by flash chromatography on silica gel (50 g) with methanol/EE (1:3, 440 ml) and the non-polar diastereoisomer of 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide (266 mg) was isolated in the form of a crystalline solid. 265 mg (6 mmol.) thereof were dissolved in 2-butanone, and chlorotrimethylsilane (113 μl, 0.9 mmol.) was added thereto. A colourless, tacky precipitate immediately formed and was converted into a fine pale-pink solid by the addition of ether. The solid was filtered off, washed with cold ether (3×2 ml) and dried in vacuo. The hydrochloride of 6-(1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide was thus obtained in a yield of 274 mg (pale-pink solid, m.p. 120–125° C.).

Workup

  1. concentrationthe mixture was concentrated
  2. extractionextracted with EE (4×10 ml)
  3. washThe combined organic extracts were washed with 1M NaOH (2×2 ml)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel (50 g) with methanol/EE (1:3, 440 ml)

Sources & evidence

ORD record
ord-344e4a4c2f9f4a61b6bc7312a9422f2b
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Linked notes

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