Methanesulfonamide → HCID 11642712, compound

HRID 2110756Notes

Reaction equation

HRID 2110756 reaction equation
CCN=C=NCCCN(C)C.Cl.[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[CH2:21][CH2:22][NH:23][C:24]1[N:29]=[C:28]([O:30][CH3:31])[N:27]=[C:26]([C:32]2[CH:33]=[C:34]([C:38]3([C:44](O)=[O:45])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:35]=[CH:36][CH:37]=2)[CH:25]=1.[CH3:47][S:48]([NH2:51])(=[O:50])=[O:49]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[CH2:21][CH2:22][NH:23][C:24]1[N:29]=[C:28]([O:30][CH3:31])[N:27]=[C:26]([C:32]2[CH:33]=[C:34]([C:38]3([C:44]([NH:51][S:48]([CH3:47])(=[O:50])=[O:49])=[O:45])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:35]=[CH:36][CH:37]=2)[CH:25]=1

Participants

6

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11584210HCID 11584210, compound

Product 1

HCID 11642712HCID 11642712, compoundYield 37.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (60.4 mg, 0.31 mmol) is added to a stirred ice cold solution of 4-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid [150 mg, 0.3 mmol, Example 80(a)], methanesulfonamide (30 mg, 0.31 mmol) and 4-dimethylaminopyridine (38.5 mg, 0.3 mmol) in dry DCM under nitrogen and the reaction mixture is stirred overnight, while warming to room temperature. The mixture is concentrated in vacuo, the residue is dissolved in ethyl acetate, washed with 0.1 N HCl, brine and water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography (SiO2 packed column), eluting with ethyl acetate/heptane to afford N-[4-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carbonyl]-methanesulfonamide [65 mg, Example 80(b)] . LCMS: RT=2.54 minutes; MS: 579, 581 (M+H); 1H NMR (300 MHz, CDCl3): □8 (1H, s), 7.85 (1H, d, J=3.5 Hz), 7.45 (3H, m), 7.2 (2H, s), 6.4 (1H, s), 5.38 (1H, b), 4 (3H, s), 3.65-3.9 (6H, m), 3.2 (3H, s), 3.08 (2H, t, J=3.5 Hz), 2.45 (2H, b), 2.18 (2H, m). IC50<1 nM

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. dissolutionthe residue is dissolved in ethyl acetate
  3. washwashed with 0.1 N HCl, brine and water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by chromatography (SiO2 packed column)
  8. washeluting with ethyl acetate/heptane

Sources & evidence

ORD record
ord-5473e533322b4ea5ac9f25030088d662
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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