Water → 1-(4-cyclobutyl-piperazin-1-yl)-2-[6-(pyrrolidine-1-carbonyl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethanone

HRID 1713105Notes

Reaction equation

HRID 1713105 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:26])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([C:23](O)=[O:24])[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.O>C(Cl)Cl>[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:26])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([C:23]([N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)=[O:24])[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 31268PyrrolidineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 574211272-[2-(4-Cyclobutyl-piperazin-1-yl)-2-oxo-ethyl]-1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid

Product 1

HCID 247515121-(4-cyclobutyl-piperazin-1-yl)-2-[6-(pyrrolidine-1-carbonyl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-[2-(4-cyclobutyl-piperazin-1-yl)-2-oxo-ethyl]-1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid (179 mg, 0.5 mmol) and pyrrolidine (71 mg, 1.0 mmol, 2.0 eq.) in DCM (5.0 ml) are added BOP (265 mg, 0.6 mmol, 1.2 eq.) and TEA (101 mg, 1 mmol, 2.0 eq.). The mixture is stirred at rt for 2 hr. Water (5.0 ml) is added to quench the reaction, and the organic layer is collected, dried over sodium sulfate, and concentrated. The residue is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.23-7.30 (2H, m), 7.01 (1H, d), 3.69 (2H, s), 3.55-3.66 (6H, m), 3.40 (2H, t), 3.35 (2H, s), 2.90 (2H, t), 2.78 (2H, t), 2.66 (1H, m), 2.26 (4H, m), 1.60-2.05 (10H, m); MS (+VE) m/z 411.1 (M++1).

Workup

  1. customto quench
  2. customthe reaction
  3. customthe organic layer is collected
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue is purified by PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-549451e3855b4792af4dae3a575f0496
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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