Triethylamine → HCID 19601678, compound

HRID 610657Notes

Reaction equation

HRID 610657 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18]([OH:20])=O)[N:9]=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:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18]([N:49]([CH3:48])[CH:50]([CH2:52][CH2:53][F:21])[CH3:51])=[O:20])[N:9]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 19601667HCID 19601667, compoundHCID 54530985HCID 54530985, compound

Product 1

HCID 19601678HCID 19601678, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-(2-iodophenyl)-3-isoquinolinecarboxylic acid (54.4 mg, 0.15 mmol), BOP (65.4 mg, 0.15 mmol) in DMF (6 mL) under Ar was added a solution of N-methyl 3-fluoro-2-butylamine (333.3 mg, crude, excess) and Et3N (21 μL, 0.15 mmol) in DMF (1.0 mL). The resulting mixture was stirred at ambient temperature for 7 h. Then it was quenched by adding H,O (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 (36.2 mg). This oil was further purified on reverse phase HPLC (75% MeOH/H2O, 0.1% Et3N). Two major fractions were collected. The first fraction (Rt=13 min, 12 mg, 17%) was the title compound. mp 62-63.5° C. 1H NMR (CDCl3) d 1.20-1.40 (m, 3 H, CH3), 1.72-2.30 (m, 2 H, CH2), 3.01, 3.02 (two s, total 3 H, N-methyl), 4.32-4.57 (m, 2 H, CH2F), 4.60-4.71 (m, 0.5 H, CH), 4.92-5.02 (m, 0.5 H, CH), 7.21 (t, J=7.2 Hz, 1 H, aromatic), 7.32 (d, J=7.8 Hz, 1 H, aromatic), 7.46-7.64 (m, 3 H, aromatic), 7.72-7.83 (m, 1 H, aromatic), 7.95-8-19 (m, 3 H, aromatic). HRMS Cacld for C21H20FIN2O: 462.0604. Found: 462.0598.

Workup

  1. customThen it was quenched
  2. additionby adding H,O (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-00ba8f18c58643f78dbc8ff8700f8f04
Source dataset
uspto-grants-1999_12
Patent number
US05998624

Reaction notes

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