Triethylamine → HCID 19601679, compound

HRID 610658Notes

Reaction equation

HRID 610658 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([OH:20])=O)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:21][P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:48][NH:49][CH:50]([CH:52](F)[CH3:53])[CH3:51].CCN(CC)CC>CN(C=O)C>[I:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([N:49]([CH3:48])[CH:50]([CH2:52][CH2:53][F:21])[CH3:51])=[O:20])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 19601657HCID 19601657, compoundHCID 54530985HCID 54530985, compound

Product 1

HCID 19601679HCID 19601679, compoundYield 63.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-(3-iodophenyl)-3-isoquinolinecarboxylic acid (52.2 mg, 0.14 mmol), BOP (64.2 mg, 0.15 mmol) in DMF (6 mL) under Ar was added a solution of N-methyl 3-fluoro-2-butylamine (420 mg, crude, excess) and Et3N (20 μL, 0.14 mmol) in DMF (1.0 mL). The resulting mixture was stirred at ambient temperature for 7 h. Then it was quenched by adding H2O (5 mL). The mixture was extracted with CH2Cl2 (3×20 mL). The organic layers were dried (Na2SO4), filtered. The filtrate was concentrated in vacuo. The residue was purified on column chromatography (silica gel, 30% ethyl acetate/hexane, 0.05% Et3N) to give a yellow oil (41.1 mg). This oil was further purified on reverse phase HPLC (75% MeOH/H2O, 0.1% Et3N). After reverse phase HPLC purification, a pale yellow solid (17 mg, 26%) was obtained. mp 50-51.5° C. 1H NMR (CDCl3) d 1.24-1.41 (m, 3 H, CH3), 1.75-2.21 (m, 2 H, CH2), 2.98, 3.01 (two s, total 3 H, N-methyl), 4.29-4.40 (m, 1 H, CH2F), 4.44-4.58 (m, 1 H, CH2F), 4.63-4.74 (m, 0.5 H, CH), 4.96-5.06 (m, 0.5 H, CH), 7.27 (dt, J=9.6, 1.8 Hz, 1 H, aromatic), 7.58-7.64 (m, 2 H, aromatic), 7.74 (t, J=6.9 Hz, 1 H, aromatic), 7.85 (d, J=7.8 Hz, 1 H, aromatic), 7.95 (d, J=8.1 Hz, 1 H, aromatic), 8.01-8.12 (m, 3 H, aromatic). HRMS Cacld for C21H20FIN2O: 462.0604. Found: 462.0607.

Workup

  1. customThen it was quenched
  2. additionby adding H2O (5 mL)
  3. extractionThe mixture was extracted with CH2Cl2 (3×20 mL)
  4. dry with materialThe organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe residue was purified on column chromatography (silica gel, 30% ethyl acetate/hexane, 0.05% Et3N)

Sources & evidence

ORD record
ord-c5fbd7a34d9d4e738088933df2e3eef9
Source dataset
uspto-grants-1999_12
Patent number
US05998624

Reaction notes

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