Diisopropylethylamine → 2-(4-Methoxy-5-nitrophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]-acetamide

HRID 353268Notes

Reaction equation

HRID 353268 reaction equation
[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][C:6]([CH2:12][C:13]([OH:15])=O)=[CH:5][CH:4]=1.O.ON1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2N=N1.Cl.[CH3:28][N:29]([CH3:38])[CH2:30][CH2:31][CH2:32]N=C=NCC.[CH:39]([N:42](CC)[CH:43](C)C)(C)C>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][C:6]([CH2:12][C:13]([N:42]([CH3:43])[C@@H:39]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:38][N:29]2[CH2:28][CH2:32][CH2:31][CH2:30]2)=[O:15])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 43305212-(4-Methoxy-3-nitrophenyl)acetic acid

Product 1

HCID 697950522-(4-Methoxy-5-nitrophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]-acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of acid (iii)(17.5 g, 85.78 mmol) in anhydrous CH2Cl2 (175 mL) was added 1-hydroxybenzotriazole hydrate (11.58 g, 85.78 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 18.02 g, 94.36 mmol). After stirring the reaction mixture at room temperature for 30 min, a solution of the diamine (iv-a)(16.00 g, 78.43 mmol) in anhydrous CH2Cl2 (60 mL) was added, followed by N,N-diisopropylethylamine (10.43 g, 80.0 mmol). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was quenched with saturated sodium bicarbonate solution and the organic layer was separated, washed with saturated salt solution and dried over anhydrous sodium sulfate. The removal of CH2Cl2 under reduced pressure gave crude compound (v-a) as dark brown oil. The product (v-a) was purified on a silica gel column to give a yellow syrup, 31 g (99%); 1HNMR (CDCl3, 300 MHz) δ1.74 (m, 4H), 2.75 (s, 3H), 3.95 (s, 3H), 6.10 (m, 1H), 7.05-7.75 (m, 8H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 72 h
  2. customThe reaction mixture was quenched with saturated sodium bicarbonate solution
  3. customthe organic layer was separated
  4. washwashed with saturated salt solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe removal of CH2Cl2 under reduced pressure
  7. customgave crude compound (v-a) as dark brown oil
  8. customThe product (v-a) was purified on a silica gel column
  9. customto give a yellow syrup, 31 g (99%)

Sources & evidence

ORD record
ord-6c970fce228f4ce1b4ea543013cb5678
Source dataset
uspto-grants-2004_06
Patent number
US06750216B2

Reaction notes

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