Cyclopropanemethanamine → HCID 67189000, compound

HRID 546108Notes

Reaction equation

HRID 546108 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(NC2C=CN(CC3C=[C:60]([CH:64]=[CH:65]C=3)[C:61]([NH2:63])=O)N=2)=O)C=CC=1S(C)(=O)=O.NCC1CC1>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:63][CH2:61][CH:60]3[CH2:64][CH2:65]3)=[O:26])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

5

Reactant 3

HCID 75646CyclopropanemethanamineHCID 67189846HCID 67189846, compoundHCID 86618046HCID 86618046, compound

Product 1

HCID 67189000HCID 67189000, compoundYield 36%

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 aminomethyl cyclopropane (20 mg, 0.28 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-cyclopropylmethyl-benzamide (60 mg, 36%) as a white powder: ESI-LRMS m/e calcd for C30H35ClN4O4S [M+] 582.21, found 583.33 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.17-0.27 (m, 2H, CH2), 0.39-0.046 (m, 2H, CH2), 0.98-1.17 (m, 3H, CH and CH2), 1.37-1.78 (m, 8H, 4×CH2), 2.02-2.17 (m, 1H, CH), 3.12 (t, J=6.0 Hz, 2H, NCH2), 3.32 (s, 3H, SO2CH3), 3.83-3.91 (m, 1H, CH), 5.22 (s, 2H, NCH2), 6.46 (d, J=2.0 Hz, 1H, Ar), 7.28-7.36 (m, 1H, Ar), 7.39 (t, J=8.0 Hz, 1H, Ar), 7.56 (d, Jo=7.8 Hz, 1H, Ar), 7.65 (d, Jm=1.2 Hz, 1H, Ar), 7.69-7.80 (m, 3H, Ar), 7.97 (d, Jo=8.2 Hz, 1H, Ar), 8.51 (m, 1H, NH), 10.77 (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-235615722bb94ac0bdfad71e9d39aec2
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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