Triethylamine → (S)-2-(3-Aminomethyl-oxetan-3-ylamino)-N-(3,4-dimethyl-phenyl)-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]acetamide

HRID 1094342Notes

Reaction equation

HRID 1094342 reaction equation
[NH2:1][C@@H:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:3]([N:5]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=1)[CH2:6][CH2:7][C:8]1[CH:9]=[N:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=1)=[O:4].[N+:32]([CH:35]=[C:36]1[CH2:39][O:38][CH2:37]1)([O-])=O.CCN(CC)CC>C(Cl)Cl>[NH2:32][CH2:35][C:36]1([NH:1][C@@H:2]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:3]([N:5]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=2)[CH2:6][CH2:7][C:8]2[CH:9]=[N:10][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:12][CH:13]=2)=[O:4])[CH2:39][O:38][CH2:37]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 44546187(S)-2-amino-N-(3,4-dimethyl-phenyl)-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamideHCID 533465963-(Nitromethylidene)oxetane

Product 1

HCID 58007567(S)-2-(3-Aminomethyl-oxetan-3-ylamino)-N-(3,4-dimethyl-phenyl)-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]acetamideYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-amino-N-(3,4-dimethyl-phenyl)-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide (50 mg, 0.11 mmol, prepared as in example 1) and 3-nitromethylene-oxetane (12 mg, 0.104 mmol, [CAS No. 922500-95-6]) in CH2Cl2 (0.5 mL) was treated with Et3N (11 mg, 0.11 mmol) at 0° C. After stirring for 30 min at ambient temperature, the mixture was concentrated, dissolved in MeOH (1 mL) and treated with a solution of HCO2NH4 (300 mg, 4.76 mmol) in H2O (0.5 mL), 10% Pd/C (100 mg) and the mixture stirred for 12 h at ambient temperature. After the addition of 1N Na2CO3 (15 mL), the aqueous layers were filtered then extracted with CH2Cl2 (3×15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, CH2Cl2:MeOH=100:0 to 90:10) afforded the title compound (26 mg, 46%) as a light yellow oil. MS m/e: 513.5 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutiondissolved in MeOH (1 mL)
  3. additiontreated with a solution of HCO2NH4 (300 mg, 4.76 mmol) in H2O (0.5 mL)
  4. stirring10% Pd/C (100 mg) and the mixture stirred for 12 h at ambient temperature
  5. additionAfter the addition of 1N Na2CO3 (15 mL)
  6. filtrationthe aqueous layers were filtered
  7. extractionthen extracted with CH2Cl2 (3×15 mL)
  8. dry with materialthe combined organic layers dried over sodium sulfate
  9. concentrationConcentration and purification by chromatography (SiO2, CH2Cl2:MeOH=100:0 to 90:10)

Sources & evidence

ORD record
ord-02a3bfa12858487fbf95587cadbacf9e
Source dataset
uspto-grants-2012_03
Patent number
US08133909B2

Reaction notes

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