Water → HCID 24889831, compound

HRID 546106Notes

Reaction equation

HRID 546106 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:31][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25](Cl)=[O:26])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].ClC1C=C([C@@H](CC2CCCC2)[C:49]([NH:51]C2C=CN(CC3C=C(C=CC=3)C(N)=O)N=2)=O)C=CC=1S(C)(=O)=O.CN.O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:31][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25]([NH:51][CH3:49])=[O:26])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 67189846HCID 67189846, compoundHCID 86618046HCID 86618046, compound

Product 1

HCID 24889831HCID 24889831, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a 0.166 M solution of crude 3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoyl chloride in methylene chloride (prepared in Example 63, 1.71 mL, 0.28 mmol) was added a 40% solution of methylamine in water (250 μL, 0.32 mmol) and the reaction stirred at 25° C. for 30 min. The solution was diluted with methylene chloride (40 mL), washed with water (2×20 mL), saturated aqueous brine solution (2×20 mL), dried over magnesium sulfate and concentrated in vacuo to an off white foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 100% ethyl acetate/methylene chloride) afforded 3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-N-methyl-benzamide (61 mg, 39%) as a white powder: ESI-LRMS m/e calcd for C27H31ClN4O4S [M+] 542.18, found 543.16 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.15 (m, 2H, CH2), 1.34-1.79 (m, 8H, 4×CH2), 2.00-2.17 (m, 1H, CH), 2.75 (d, J, 4.5 Hz, 3H, NCH3), 3.32 (s, 3H, SO2CH3), 3.82-3.90 (m, 1H, CH), 5.21 (s, 2H, NCH2), 6.45 (d, J=2.3 Hz, 1H, Ar), 7.28-7.34 (m, 1H, Ar), 7.38 (t, J=7.8 Hz, 1H, Ar), 7.55 (dd, Jo=8.3, Jm=1.6 Hz, 1H, Ar), 7.65 (d, Jm=1.6 Hz, 1H, Ar), 7.67-7.71 (m, 2H, Ar), 7.72 (d, J=2.3 Hz, 1H, Ar), 7.97 (d, Jo=8.3 Hz, 1H, Ar), 8.33-8.45 (brm, 1H, NH), 10.76 (s, 1H, NH).

Workup

  1. washwashed with water (2×20 mL), saturated aqueous brine solution (2×20 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo to an off white foam
  4. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 100% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-0ad0d49d8a3345d9818b1dc489581b28
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

Loading…