1H-Indole-1-acetic acid → N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-indol-1-yl-acetamide

HRID 346798

Reaction equation

HRID 346798 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][C:46](O)=[O:47])[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:46](=[O:47])[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 904481H-Indole-1-acetic acidHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 10340305N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-indol-1-yl-acetamide

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 indol-1-ylacetic acid (350 mg, 2.0 mmol.) in abs. methanol (25 ml), and the reaction mixture was stirred 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 (3×15 ml). The combined extracts were dried, filtered and concentrated. The residue was a diastereoisomeric mixture of the bases of the target products, which was separated by flash chromatography on silica gel (70 g) and purified (eluant: methanol/EE 500 ml 1:3, then 1000 ml 1:1). 244 mg of the non-polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-indol-1-yl-acetamide were obtained in the form of a viscous oil. 50 mg (0.128 mmol.) thereof were dissolved in 2-butanone (2 ml), and chlorotrimethylsilane (24.4 μl, 0.193 mmol.) was added thereto. There immediately formed a pale precipitate, which turned a strong colour within a few minutes. The solid was filtered off with suction, washed with ether (3×0.5 ml) and dried in vacuo. The hydrochloride 7/8 of the non-polar target product was thus obtained in a yield of 52 mg (brick-red solid, m.p. 176–186° 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 diastereoisomeric mixture of the bases of the target products, which
  8. customwas separated by flash chromatography on silica gel (70 g)
  9. custompurified (eluant

Sources & evidence

ORD record
ord-8628b53339a64e838e7c56f375efc972
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Linked notes

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