Benzaldehyde → 2-Benzyl-6-({3-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2365622Notes

Reaction equation

HRID 2365622 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:17][N:16]([C:18]([C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[CH2:26][NH:25][CH2:24][CH2:23]4)=[O:19])[CH2:15]2)[CH2:10][CH2:9]1)=[O:7].[CH:30](=O)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl.O>[CH2:30]([N:25]1[CH2:24][CH2:23][C:22]2[C:27](=[CH:28][CH:29]=[C:20]([C:18]([N:16]3[CH2:17][CH:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([C:2]5[S:1][CH:5]=[CH:4][N:3]=5)=[O:7])[CH2:9][CH2:10]4)[CH2:15]3)=[O:19])[CH:21]=2)[CH2:26]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 596257876-({3-[4-(1,3-Thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 596258372-Benzyl-6-({3-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroisoquinolineYield 63.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of Cpd 916 (50 mg, 0.121 mmol) and benzaldehyde 23a (0.014 mL, 0.134 mmol) in CH2Cl2 (2 mL) was stirred at room temperature for 30 min. Sodium triacetoxyborohydride (38.6 mg, 0.182 mmol) was added and the mixture was stirred overnight. The resulting mixture was combined with CH2Cl2 and H2O, and pH of the water layer was adjusted to pH˜8 with 1N aqueous NaOH. The organic solution was dried over Na2SO4 and concentrated. Purification the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc) gave Cpd 680 (38.6 mg). 1H NMR (400 MHz, CDCl3): δ 7.89 (d, J=3.2 Hz, 1H), 7.55 (d, J=3.2 Hz, 1H), 7.32-7.44 (m, 6H), 7.3 (d, J=8.1 Hz, 1H), 7.02 (d, J=8.1 Hz, 1H), 4.33-4.63 (m, 2H), 3.99-4.34 (m, 4H), 3.75-3.98 (m, 2H), 3.70 (s, 2H), 3.65 (s, 2H), 3.16-3.30 (m, 1H), 2.93 (t, J=5.7 Hz, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.37-2.60 (m, 4H). MS m/z (M+H+) 502.0.

Workup

  1. dry with materialThe organic solution was dried over Na2SO4
  2. concentrationconcentrated
  3. customPurification the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc)

Sources & evidence

ORD record
ord-6f3a6d81a87846469623338b65bca9f8
Source dataset
uspto-grants-2014_04
Patent number
US08697683B2

Reaction notes

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