Methanesulfonamide → HCID 11642712, compound

HRID 216228Notes

Reaction equation

HRID 216228 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 0.1N 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 0.1N 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-c7cce9efceb549ec94987643e4e1c55d
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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