Chlorotrimethylsilane → HCID 10369286, compound

HRID 346804Notes

Reaction equation

HRID 346804 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.[Cl:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][CH:41]=[C:40]2[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][C:51]([OH:53])=[O:52].Cl[Si](C)(C)C>CCOCC.CO>[ClH:36].[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:51](=[O:52])[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][C:40]2[C:39]3[C:43](=[CH:44][CH:45]=[C:37]([Cl:36])[CH:38]=3)[NH:42][CH:41]=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:51](=[O:53])[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][C:40]2[C:39]3[C:43](=[CH:44][CH:45]=[C:37]([Cl:36])[CH:38]=3)[NH:42][CH:41]=2)[CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21082139HCID 21082139, compoundHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 2

HCID 10369286HCID 10369286, compoundHCID 10369287HCID 10369287, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of the diastereoisomers of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (152 mg, 0.65 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (207.5 mg, 0.75 mmol.) was added to a solution of 6-(5-chloro-1H-indol-3-yl)hexanoic acid (174 mg, 0.65 mmol.) in abs. methanol (5 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 washed with 1M NaOH (2×2 ml), dried, filtered and concentrated. The residue was a diastereoisomeric mixture of the bases of the target product, which was separated by flash chromatography on silica gel (35 g) and purified (eluant: 600 ml of methanol/EE 1:1). The resulting non-polar diastereoisomer (110 mg, 0.23 mmol.) was dissolved in 2-butanone (5 ml), and chlorotrimethylsilane (44 μl, 0.35 mmol.) was added thereto. There immediately formed a white precipitate, which after 15 min. was deposited in a tacky manner on the wall of the flask. The solvent was reduced to about 0.5 ml in vacuo, ether (2 ml) was added to the residue, and vigorous stirring was carried out for 1 h. The solid that formed was filtered off with suction, washed with ether (2×1 ml) and dried in vacuo. The hydrochloride of the non-polar diastereoisomer of 6-(5-chloro-1H-indol-3-yl)hexanoic acid (4-dimethylamino-4-phenylcyclohexylmethyl)amide was thus obtained in the form of a slightly hygroscopic solid in a yield of 124 mg (m.p. 135–145° 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. washThe combined extracts were washed with 1M NaOH (2×2 ml)
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additiona diastereoisomeric mixture of the bases of the target product, which
  9. customwas separated by flash chromatography on silica gel (35 g)
  10. custompurified (eluant: 600 ml of methanol/EE 1:1)
  11. dissolutionThe resulting non-polar diastereoisomer (110 mg, 0.23 mmol.) was dissolved in 2-butanone (5 ml)
  12. customThere immediately formed a white precipitate, which after 15 min.
  13. additionwas added to the residue
  14. waitwas carried out for 1 h
  15. customThe solid that formed
  16. filtrationwas filtered off with suction
  17. washwashed with ether (2×1 ml)
  18. customdried in vacuo

Sources & evidence

ORD record
ord-7ad09dc15c304438befa6b6d845fb9ab
Source dataset
uspto-grants-2007_02
Patent number
US07173045B2

Reaction notes

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