p-Toluenesulfonic acid monohydrate → HCID 57920037, compound

HRID 19334Notes

Reaction equation

HRID 19334 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][C@H:9]([N:26]1[CH2:30][C:29]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])=[CH:28][C:27]1=[O:39])[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH2:18][C@@H:19]2[CH2:23][O:22]C(C)(C)[O:20]2)[N:14]=1)=[O:11])(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:38][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[O:31][C:29]1[CH2:30][N:26]([C@@H:9]([CH2:8][CH2:7][OH:6])[C:10]([NH:12][C:13]2[CH:17]=[CH:16][N:15]([CH2:18][C@@H:19]([OH:20])[CH2:23][OH:22])[N:14]=2)=[O:11])[C:27](=[O:39])[CH:28]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 67503776HCID 67503776, compound

Product 1

HCID 57920037HCID 57920037, compoundYield 45.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a round bottom flask was placed (S)-4-(t-butyl-dimethyl-silanyloxy)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-butyramide (128 mg, 0.21 mmol), methanol (5 mL) and p-toluenesulfonic acid monohydrate (10 mg) and stirred at 25° C. for 16 h. The mixture was then concentrated and treated with ethyl acetate and methanol to solubilize the material and concentrated in vacuo with silica gel (1 g). Purification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate) afforded material that was not pure. A second purification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-hydroxy-butyramide (43 mg, 45%) as a white foam: HR-ES-MS m/z calculated for C20H23N4O6Cl [M+H]+ 451.1379, observed 451.1379; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.88-2.06 (m, 2H), 3.23-3.31 (m, 2H), 3.37-3.50 (m, 2H), 3.72-3.81 (m, 1H), 3.86 (dd, J=13.9, 7.9 Hz, 1H), 4.09 (dd, J=13.5, 3.9 Hz, 1H), 4.29 (d, J=18.3 Hz, 1H), 4.50-4.60 (m, 2H), 4.71 (t, J=5.6 Hz, 1H), 4.80 (s, 1H), 4.84 (dd, J=8.4, 5.4 Hz, 1H), 4.94 (d, J=5.3 Hz, 1H), 6.41 (d, J=2.1 Hz, 1H), 7.11 (d, J=7.9 Hz, 1H), 7.34-7.41 (m, 1H), 7.43-7.57 (m, 2H), 7.66 (dd, J=8.0, 1.2 Hz, 1H), 10.59 (s, 1H).

Workup

  1. customIn a round bottom flask was placed
  2. concentrationThe mixture was then concentrated
  3. additiontreated with ethyl acetate and methanol
  4. concentrationconcentrated in vacuo with silica gel (1 g)
  5. customPurification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate)
  6. customafforded material that
  7. customA second purification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-9e1ce3380f2f4873bc2cc0310fbd4186
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…