Triethylamine → 3-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-(3-hydroxyazetidin-1-yl)butyl]-N-methyl-1-naphthamide

HRID 749439Notes

Reaction equation

HRID 749439 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][C@H:18]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:19][CH:20]=O)[CH3:16])=[O:14])[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].Cl.[NH:31]1[CH2:34][CH:33]([OH:35])[CH2:32]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][C@H:18]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:19][CH2:20][N:31]2[CH2:34][CH:33]([OH:35])[CH2:32]2)[CH3:16])=[O:14])[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 187156453-Cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl)-N-methyl-1-naphthamide

Product 1

HCID 689772843-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-(3-hydroxyazetidin-1-yl)butyl]-N-methyl-1-naphthamideYield 80.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-1-naphthamide (see WO 00/02859; 1.0 g, 2.3 mmol) was dissolved in CH2Cl2 (10 mL) and to the resultant solution were added azetidin-3-ol hydrochloride (0.24 g, 2.2 mmol) and triethylamine (0.30 mL, 2.2 mmol). After stirring for 40 min, sodium triacetoxyborohydride (0.65 g, 3.1 mmol) was added and the solution was stirred at room temperature for 3 h. The solvent was removed by evaporation and the residue was partitioned between saturated aqueous NaHCO3 solution and ethyl acetate. The solvent was removed by evaporation and the residue was dissolved in hydrochloric acid (1M). The solution was washed with CH2Cl2, alkalised with aqueous NaOH (2M) and then extracted with CH2Cl2. The solvent was removed by evaporation and there was obtained 0.85 g (80%) of 3-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-(3-hydroxyazetidin-1-yl)butyl]-N-methyl-1-naphthamide as a white solid. 1H NMR (400 MHz, DMSO-d6): 0.8-4.4 (cm, 16H), 6.4-8.2 (cm, 8H), 8.6 (d, 1H); LCMS: m/z 482 (M+1)+.

Workup

  1. stirringthe solution was stirred at room temperature for 3 h
  2. customThe solvent was removed by evaporation
  3. customthe residue was partitioned between saturated aqueous NaHCO3 solution and ethyl acetate
  4. customThe solvent was removed by evaporation
  5. dissolutionthe residue was dissolved in hydrochloric acid (1M)
  6. washThe solution was washed with CH2Cl2
  7. extractionextracted with CH2Cl2
  8. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-9927ad7f3a7541ba8ed7cc0779e43518
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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