Diisopropylethylamine → HCID 178429372, compound

HRID 707366Notes

Reaction equation

HRID 707366 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[N:8]=1)(=O)=O.Cl.[NH2:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:35])([CH3:34])[C:26]2=[O:36])[CH2:22]1.C(N(CC)C(C)C)(C)C>CS(C)=O.O>[N:8]1[C:9]2[C:14](=[N:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=[CH:16][C:7]=1[NH:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:34])([CH3:35])[C:26]2=[O:36])[CH2:22]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 866942231,5-Naphthyridin-2-yl trifluoromethanesulfonateHCID 178429370HCID 178429370, compound

Product 1

HCID 178429372HCID 178429372, compoundYield 71.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To suspension of 1,5-naphthyridin-2(1H)-one (0.200 g, 1.368 mmol) in Pyridine (1 mL) was added slowly trifluoromethanesulfonic anhydride (0.050 mL, 0.298 mmol). After the addition, the reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated under high vacuum and residue diluted with water and extracted with EtOAc. EtOAc was washed with water, brine, dried over Na2SO4 and concentrated to give crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate. To this crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate (100 mg) in DMSO (0.5 mL) was added 7-(trans-3-aminocyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one hydrochloride, INTERMEDIATE 62, (0.05 g, 0.186 mmol) and N,N-diisopropylethylamine (0.032 mL, 0.186 mmol). The mixture was heated to 100° C. for 2 hours, diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO using silical gel column eluting with 0-100% EtOAc/hexanes to give the title compound 7-(trans-3-((1,5-naphthyridin-2-yl)amino)cyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (0.048 g, 0.133 mmol, 71.6% yield). m/z: 361.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85 (s, 1 H) 8.62 (dd, J=4.21, 1.27 Hz, 1 H) 8.33 (s, 1 H) 8.07 (d, J=9.00 Hz, 1 H) 7.98 (d, J=8.22 Hz, 1 H) 7.45 (dd, J=8.51, 4.21 Hz, 1 H) 6.88 (d, J=9.00 Hz, 1 H) 5.46 (d, J=4.50 Hz, 1 H) 5.17-5.35 (m, 1 H) 4.79 (dd, J=7.92, 3.62 Hz, 1 H) 3.32-3.58 (m, 2 H) 2.44 (tt, J=10.03, 3.08 Hz, 2 H) 1.45 (s, 6 H).

Workup

  1. extractionextracted with EtOAc
  2. concentrationEtOAc was concentrated
  3. customresidue purified with ISCO
  4. washeluting with 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-85d3c7d0548142238e399fc87b332d74
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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