Ethanesulfonamide → HCID 57636035, compound

HRID 216231Notes

Reaction equation

HRID 216231 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]([F:43])([F:42])[C:39](O)=[O:40])[CH:35]=[CH:36][CH:37]=2)[CH:25]=1.[CH2:44]([S:46]([NH2:49])(=[O:48])=[O:47])[CH3:45]>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]([F:42])([F:43])[C:39]([NH:49][S:46]([CH2:44][CH3:45])(=[O:48])=[O:47])=[O:40])[CH:35]=[CH:36][CH:37]=2)[CH:25]=1

Participants

6

Reactant 3

HCID 73702EthanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11540010HCID 11540010, compound

Product 1

HCID 57636035HCID 57636035, compoundYield 29.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (43 mg, 0.22 mmol) is added to a stirred ice cold solution of (3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-difluoro-acetic acid [100 mg, 0.21 mmol, Example 81 (a)], ethanesulfonamide (24.5 mg, 0.22 mmol) and 4-dimethylaminopyridine (26.1 mg, 0.21 mmol) in dry DCM under nitrogen. The reaction mixture is stirred at room temperature overnight at 60° C. 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 to afford ethanesulfonic acid [2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2,2-difluoro-acetyl]-amide [35 mg, Example 81(b)]. LCMS: RT=2.31 minutes; MS: 559, 561 (M+H); 1H NMR [300 MHz, CD3OD]: □8.18 (1H, b), 8.05 (1H, b), 7.75 (1H, d, J=4 Hz), 7.5 (1H, t, J=4 Hz), 7.42 (1H, s), 7.28 (2H, q, J=4 Hz), 6.55 (1H, s), 3.95 (3H, s), 3.7 (2H, b), 3.18 (2H, q, J=4 Hz), 3.08 (2H, t, J=3.5 Hz), 1.15 (3H, t, J=4 Hz). IC50=0.1 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

Sources & evidence

ORD record
ord-24ab9c24c6f84ee2ae35536950455a6f
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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