Indole-3-Acetic Acid → HCID 10002558, compound

HRID 346795Notes

Reaction equation

HRID 346795 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][C:46]([OH:48])=[O:47])=[CH:37]1.[Cl:49][Si](C)(C)C>CC(=O)CC.CC(C)=O.CO>[ClH:49].[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][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.[CH3:16][N:15]([CH3:17])[C:6]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:8][CH:3]([CH2:2][NH:1][C:46](=[O:48])[CH2:45][C:38]2[C:39]3[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=3)[NH:36][CH:37]=2)[CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 802Indole-3-Acetic AcidHCID 6397ChlorotrimethylsilaneHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 2

HCID 10002558HCID 10002558, compoundHCID 10002559HCID 10002559, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

The non-polar diastereoisomer of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (239 mg, 1.03 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (428 mg, 1.6 mmol.) were added to a solution of 2-(1H-indol-3-yl)acetic acid (180 mg, 1.03 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 (20 ml); 2M HCl (1.5 ml, pH 3) was added, with stirring, and washing was carried out with ether (3×5 ml). The aqueous phase was adjusted to pH 11 with 5M NaOH and extracted with EE (4×10 ml). The organic phase was washed with 1M NaOH (3 ml), dried, filtered and concentrated. The residue was the non-polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-(1H-indol-3-yl)acetamide, which was obtained in the form of a solid in a yield of 395 mg (98%). These 395 mg (1.01 mmol.) were dissolved in 2-butanone (5 ml) and acetone (3 ml), and chlorotrimethylsilane (193 μl, 1.52 mmol.) was added thereto. There immediately formed a colourless precipitate, which turned slightly beige in colour at RT. The precipitate was filtered off, washed with cold 2-butanone (2×1 ml) and cold ether (2×2 ml) and dried in vacuo. The hydrochloride of N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-(1H-indol-3-yl)acetamide was obtained in a yield of 341 mg (light-beige solid, m.p. 128–135° C.).

Workup

  1. concentrationthe mixture was concentrated
  2. addition2M HCl (1.5 ml, pH 3) was added
  3. washwashing
  4. extractionextracted with EE (4×10 ml)
  5. washThe organic phase was washed with 1M NaOH (3 ml)
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customwhich was obtained in the form of a solid in a yield of 395 mg (98%)
  10. customThere immediately formed a colourless precipitate, which
  11. customturned slightly beige in colour at RT
  12. filtrationThe precipitate was filtered off
  13. washwashed with cold 2-butanone (2×1 ml) and cold ether (2×2 ml)
  14. customdried in vacuo

Sources & evidence

ORD record
ord-54abec5bfcdc48718a26e3a4afb5888a
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Reaction notes

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