p-Toluenesulfonic acid → HCID 51029626, compound

HRID 2036806Notes

Reaction equation

HRID 2036806 reaction equation
CC1(C)[O:7][CH2:6][CH:5]([C:8]2[CH:9]=[C:10]([C:14]3[N:23]=[C:22]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][C:20]=4[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:15]=3)[CH:11]=[N:12][CH:13]=2)[CH2:4][O:3]1.CC1C=CC(S(O)(=O)=O)=CC=1>CO>[C:32]1([C:20]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:21]=2[C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[N:23][C:14]([C:10]2[CH:9]=[C:8]([CH:5]([CH2:4][OH:3])[CH2:6][OH:7])[CH:13]=[N:12][CH:11]=2)=[N:15]3)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 67055874HCID 67055874, compound

Product 1

HCID 51029626HCID 51029626, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution 2-(5-(2,2-dimethyl-1,3-dioxan-5-yl)pyridin-3-yl)-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (45 mg, 0.83 mmol) in methanol (5 mL) was added pTSA (30 mg, 0.17 mmol) and the mixture was stirred for 2 h. The reaction was quenched by the addition of sat. Na2CO3 solution and the volatile solvents removed under reduced pressure. The residue was dissolved in ethyl acetate then washed with water and brine. The organic layer was dried, concentrated and purified by filter column 80% EtOAc in Hexanes to provide 2-(5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridin-3-yl)propane-1,3-diol (18 mg, 44%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.74 (s, 1H), 9.60 (d, 1H, J=2 Hz), 9.56 (d, 1H, J=2 Hz), 8.26 (d, 1H, J=4.8 Hz), 7.90 (dd, 1H, J=1.2, 9.2 Hz), 7.83 (t, 1H, J=7.2 Hz), 7.72 (dd, 1H, J=1.8, 7.6 Hz), 7.61-7.50 (m, 5H), 7.38-7.30 (m, 2H), 7.26 (dt, 1H, J=1.2, 8 Hz), 6.80 (br s, 1H), 4.74 (d, 1H, J=4.4 Hz), 4.70 (t, 1H, J=5.2 Hz), 3.85-3.77 (m, 2H), 3.76-3.68 (m, 2H), 3.30-2.95 (m, 1H). LCMS Method T: retention time 1.40 min; [M+1]=464.2; HPLC Method A4: purity 99.4%, retention time=5.48 min.

Workup

  1. customThe reaction was quenched by the addition of sat. Na2CO3 solution
  2. customthe volatile solvents removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthen washed with water and brine
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. custompurified
  8. filtrationby filter column 80% EtOAc in Hexanes

Sources & evidence

ORD record
ord-bf8a6b6d86ef473ba8307b50f1db9a4b
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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