1-Adamantaneacetyl chloride → N-[1-(hydroxymethyl)-2-phenylethyl]-alpha-methyl-alpha-[[tricyclo[3.3.1.13,7]dec-1-ylacetyl)-amino]-1H-indole-3-propanamide

HRID 1198065Notes

Reaction equation

HRID 1198065 reaction equation
[CH3:1][C@:2]([C:14]([NH:16][C@H:17]([CH2:25][OH:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15])([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)[NH2:3].[C:27]12([CH2:37][C:38](Cl)=[O:39])[CH2:36][CH:31]3[CH2:32][CH:33]([CH2:35][CH:29]([CH2:30]3)[CH2:28]1)[CH2:34]2>C1COCC1>[OH:26][CH2:25][CH:17]([NH:16][C:14](=[O:15])[C:2]([CH3:1])([NH:3][C:38](=[O:39])[CH2:37][C:27]12[CH2:36][CH:31]3[CH2:30][CH:29]([CH2:35][CH:33]([CH2:32]3)[CH2:34]1)[CH2:28]2)[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 27718821-Adamantaneacetyl chlorideHCID 54471265alpha-methyl-D-tryptophyl-L-phenylalaninol

Product 1

HCID 53928863N-[1-(hydroxymethyl)-2-phenylethyl]-alpha-methyl-alpha-[[tricyclo[3.3.1.13,7]dec-1-ylacetyl)-amino]-1H-indole-3-propanamideYield 113%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of α-methyl-D-tryptophyl-L-phenylalaninol (1 g, 2.85 mmol) and 4-N,N-dimethylaminopyridine (0.35 g, 2.87 mmol) in dry THF (50 mL) at 0° C. was treated dropwise, with stirring, with a solution of 1-adamantylacetyl chloride (0.605 g, 2.85 mmol). A precipitate formed immediately. The reaction mixture was left until all starting materials were consumed as assayed by TLC and IR spectroscopy. The final TLC showed three spots (10% MeOH:90% CH2Cl2). The reaction mixture was washed with 1M citric acid solution and extracted into ethyl acetate. The organic phase was then washed with water and dried over MgSO4. Concentration in vacuo gave a syrup (1.7 g) which was chromatographed over silica using 2% MeOH:98% CH2Cl2 as eluant to yield the title compound (1.35 g, 90%) as a white solid crystallized from ethyl acetate-hexane, mp 91°-94° C. (EtOAc-hexane); IR (KBr) 3304 and 1652 cm- 1 ; NMR (CDCl3) δ 1.48 (9H, m), 1.59 (6H, m), 1.76 (2H, q, J 13 Hz), 1.9 (3H, m), 2.74 (2H, d, J 7 Hz),3.21 (1H, half Abq J 14.5 Hz), 3.30 (1H, 6, J 6 Hz), 3.40 (1H, half Abq J 14.5 Hz), 3.45 (1H, m), 3.70 (1H, m), 4.16 (1H, m), 5.91 (1H, s), 6.38 (1H, d, J 8 Hz), 6.92 (1H, d, J 3 Hz), 7.07-7.27 (7 H, m), 7.35 (1H, d, J 8 Hz), 7.56 (1H, d, J 8 Hz), and 8.54 (1H, s); Anal. (C33H41N3O3.0.25 H2O), C, H, N.

Workup

  1. customA precipitate formed immediately
  2. waitThe reaction mixture was left until all starting materials
  3. customwere consumed
  4. washThe reaction mixture was washed with 1M citric acid solution
  5. extractionextracted into ethyl acetate
  6. washThe organic phase was then washed with water
  7. dry with materialdried over MgSO4
  8. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-2a3020b462d044f1aea0360b8983342d
Source dataset
uspto-grants-1994_01
Patent number
US05278316

Reaction notes

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