m-Tolyl isocyanate → HCID 71738047, compound

HRID 338755Notes

Reaction equation

HRID 338755 reaction equation
Cl.Cl.[CH2:3]1[C:12]2[C:7](=[CH:8][CH:9]=[N:10][CH:11]=2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1.C(N(CC)C(C)C)(C)C.[C:29]1([CH3:38])[CH:34]=[CH:33][CH:32]=[C:31]([N:35]=[C:36]=[O:37])[CH:30]=1>C(Cl)Cl>[CH2:3]1[C:12]2[C:7](=[CH:8][CH:9]=[N:10][CH:11]=2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:36]([NH:35][C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([CH3:38])[CH:30]=2)=[O:37])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 69303m-Tolyl isocyanateHCID 81531DiisopropylethylamineHCID 86695868HCID 86695868, compound

Product 1

HCID 71738047HCID 71738047, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)aniline dihydrochloride (75.0 mg, 0.251 mmol) and N,N-diisopropylethylamine (0.109 mL, 0.63 mmol) in 3.0 mL CH2Cl2 at rt was added meta-tolyl isocyanate (0.047 mL, 0.377 mmol) and the reaction stirred at rt for 2 hours. The reaction was quenched with 1.0 mL MeOH, stirred for 15 min and then evaporated. The sample was partitioned between EtOAc and H2O/brine mixture, the EtOAc layer washed with aqueous Na2CO3 solution, brine, dried with anhydrous Na2SO4, and evaporated to a tan solid. The solid was chromatographed eluting with CH2Cl2, EtOAc, then 3% MeOH/EtOAc to give the title compound as a white solid (79 mg, 88%). 1H NMR (DMSO-d6) δ: 8.45 (s, 1H), 8.42 (s, 1H), 8.37 (s, 1H), 8.31 (d, J=5.0 Hz, 1H), 7.29-7.35 (m, 2H), 7.28 (s, 1H), 7.16-7.23 (m, 2H), 7.10-7.16 (m, 1H), 6.96-7.02 (m, 2H), 6.76 (d, J=7.0 Hz, 1H), 4.33 (s, 2H), 3.47 (t, J=5.9 Hz, 2H), 2.91 (t, J=5.7 Hz, 2H), 2.27 (s, 3H).

Workup

  1. customThe reaction was quenched with 1.0 mL MeOH
  2. stirringstirred for 15 min
  3. customevaporated
  4. customThe sample was partitioned between EtOAc and H2O/brine mixture
  5. washthe EtOAc layer washed with aqueous Na2CO3 solution, brine
  6. dry with materialdried with anhydrous Na2SO4
  7. customevaporated to a tan solid
  8. customThe solid was chromatographed
  9. washeluting with CH2Cl2, EtOAc

Sources & evidence

ORD record
ord-672bfc0ab9c84b9c93b4758929fc7630
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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