Trifluoroacetic acid → HCID 59364339, compound

HRID 426066Notes

Reaction equation

HRID 426066 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][CH2:10][CH2:11][C@:12]1([CH2:23][CH2:24][N:25]([CH3:33])C(=O)OC(C)(C)C)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:21])[CH:19]=2)[C:14](=[O:22])[NH:13]1.C(N(CC)CC)C.[CH3:41][O:42][C:43](Cl)=[O:44].C(O)(C(F)(F)F)=O>ClCCl.CO>[Cl:21][C:18]1[CH:19]=[C:20]2[C:15]([C:14](=[O:22])[NH:13][C@@:12]2([CH2:11][CH2:10][CH2:9][NH:8][C:43](=[O:44])[O:42][CH3:41])[CH2:23][CH2:24][NH:25][CH3:33])=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 66704570HCID 66704570, compound

Product 1

HCID 59364339HCID 59364339, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 2-(1-(3-aminopropyl)-6-chloro-3-oxoisoindolin-1-yl)ethyl(methyl)carbamate trifluoroacetic acid salt (71 mg, 0.14 mmol) in dry dichloromethane (10 mL) at room temperature was added triethylamine (56 mg, 0.56 mmol) and methylchloroformate (26 mg, 0.3 mmol). After stirring for 1.5 h, methanol (2 mL) was added. The reaction mixture was stirred for 2 h and then concentrated. The residue was dissolved in dichloromethane (3 mL) and added trifluoroacetic acid (5 mL). After stirring for 2 h, the solvent and excess reagent were evaporated under reduced pressure. The residue was purified by preparative HPLC (C-18 column, 5 to 70% CH3CN in H2O containing 0.01% CF3CO2H over 20 min, 20 mL min−1) to afford product and a minor amount of (R) isomer as TFA salt (45 mg, 69%). 1H NMR (CD3OD) δ 7.73 (d, J=7.9 Hz, 1H), 7.65 (d, J=1.8 Hz, 1H), 7.56 (dd, J=8.2, 1.2 Hz, 1H), 3.58 (s, 3H), 3.00 (t, J=7.0 Hz, 2H), 2.80-2.88 (m, 1H), 2.60 (s, 3H), 2.40-2.49 (m, 1H), 2.26-2.37 (m, 2H) 1.90-2.02 (m, 2H) 1.24-1.38 (m, 1H) 0.83-0.96 (m, 1H); MS EI m/z 340 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane (3 mL)
  4. additionadded trifluoroacetic acid (5 mL)
  5. stirringAfter stirring for 2 h
  6. customthe solvent and excess reagent were evaporated under reduced pressure
  7. customThe residue was purified by preparative HPLC (C-18 column, 5 to 70% CH3CN in H2O containing 0.01% CF3CO2H over 20 min, 20 mL min−1)
  8. customto afford product

Sources & evidence

ORD record
ord-7c82f28c89c9415daa57414cdb3e2f7c
Source dataset
uspto-grants-2012_01
Patent number
US08106221B2

Reaction notes

Loading…