Dimethylformamide → HCID 59297029, compound

HRID 2234260Notes

Reaction equation

HRID 2234260 reaction equation
[CH:1]1([O:7][C:8](=[O:32])[NH:9][CH:10]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:20]4[N:21]=[N:22][NH:23][N:24]=4)[CH:17]=3)[N:12]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:33]N(C=O)C.C([O-])([O-])=O.[Cs+].[Cs+].IC>CC#N.O.C1COCC1>[CH:1]1([O:7][C:8](=[O:32])[NH:9][CH:10]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:20]4[N:21]=[N:22][N:23]([CH3:33])[N:24]=4)[CH:17]=3)[N:12]([CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 59297066HCID 59297066, compound

Product 1

HCID 59297029HCID 59297029, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of [1-benzyl-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydroquinolin-3-yl]-carbamic acid cyclohexyl ester (61 mg, 0.14 mmol), prepared as described in Example 53, in CH3CN (0.5 mL)-DMF (0.5 mL)-THF (0.5 mL) at RT was added Cs2CO3 (63.4 mg, 0.19 mmol), followed by iodomethane (7.8 μL, 0.126 mmol). The reaction mixture was stirred at RT for 16 h and then diluted with H2O, extracted with EtOAc (10 mL×3). The organic extracts were washed saturated aqueous NaCl, dried Na2SO4), and concentrated. The resulting residue was purified using preparative HPLC [YMC S5 ODS (20×100 mm); Eluted with 50% to 90% B, 8 min gradient and 7 min hold. (A=90% H2O-10% MeOH and B=10% H2O-90% MeOH); Flow rate at 20 mL/min. UV detection at 220 nm] to give the title compound (regioisomer A, 35 mg, 56%) as a white solid. HPLC (method B): 98% pure, retention time=7.9 min. MS (ES): m/z 447 [M+H]+.

Workup

  1. customat RT
  2. extractionextracted with EtOAc (10 mL×3)
  3. washThe organic extracts were washed saturated aqueous NaCl, dried Na2SO4), and
  4. concentrationconcentrated
  5. customThe resulting residue was purified
  6. washEluted with 50% to 90% B, 8 min gradient and 7 min hold

Sources & evidence

ORD record
ord-a0bc3478618c488c9860c4d99d184644
Source dataset
uspto-grants-2010_05
Patent number
US07709647B2

Reaction notes

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