p-Toluenesulfonic acid monohydrate → HCID 25060145, compound

HRID 591131

Reaction equation

HRID 591131 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([N:14]([CH2:19][C:20]#[N:21])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[CH:25][C:26]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[C:20]([CH2:19][N:14]([C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([N:32]4[CH2:33][CH2:34][O:35][CH2:36][CH2:37]4)=[C:27]([CH:31]=3)[C:28]([OH:30])=[O:29])[N:7]=2)=[CH:9][CH:10]=1)[S:15]([CH3:18])(=[O:17])=[O:16])#[N:21]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 6137005-Amino-2-morpholinobenzenecarboxylic acidHCID 86706917HCID 86706917, compound

Product 1

HCID 25060145HCID 25060145, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

N-(4-(2-chloropyrimidin-4-yl)phenyl)-N-(cyanomethyl)methanesulfonamide (171 mg, 0.53 mmol), 5-amino-2-morpholinobenzoic acid (142 mg, 1.2 eq.) and p-toluene sulfonic acid monohydrate (98 mg, 0.98 eq.) were suspended in 1,4-dioxane (8 mL) and heated at 100° C. overnight. The reaction mixture was cooled to room temperature, concentrated in vacuo. The residue was taken up in ethyl acetate (80 mL) and washed with water (20 mL) and brine (20 mL). The organic phase was then dried and concentrated in vacuo. The residue was repeatedly triturated with methanol (5 mL then 3 mL) to afford, as a cream solid, 5-(4-(4-(N-(cyanomethyl)methylsulfonamido)phenyl)pyrimidin-2-ylamino)-2-morpholinobenzoic acid (101 mg, 37%). 1H NMR (300 MHz, d6-DMSO) δ 17.23 (1H, s) CO2H, 9.99 (1H, s); 8.74 (1H, d, J=2.7 Hz); 8.62 (1H, d, J=5.0 Hz); 8.33 (2H, d, J=8.7 Hz); 8.01 (1H, dd, J=2.8, J=8.7 Hz); 7.69 (1H, d, J=9.1 Hz); 7.63 (2H, d, J=8.7 Hz); 7.52 (1H, d, J=9.1 Hz); 4.97 (2H, s); 3.81 (4H, m); 3.21 (3H, s); 3.06 (4H, m). LC-ESI-MS (method C): rt 5.4 min.; m/z 509.3 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. washwashed with water (20 mL) and brine (20 mL)
  4. customThe organic phase was then dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was repeatedly triturated with methanol (5 mL

Sources & evidence

ORD record
ord-4bf3cff8d1e145e7af62e8eec16d2b87
Source dataset
uspto-grants-2016_01
Patent number
US09238628B2

Linked notes

Loading…