Tetrahydrofuran → 4-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenyl]ureido}pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzene-sulfonamide

HRID 221911Notes

Reaction equation

HRID 221911 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=[C:4]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=1.[F:30][C:31]1[CH:36]=[C:35]([O:37][C:38]2[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=2)[CH:34]=[CH:33][C:32]=1[NH2:45].C1C[O:49][CH2:48]C1>ClCCCl>[C:26]([C:4]1[CH:3]=[C:2]([NH:1][C:48]([NH:45][C:32]2[CH:33]=[CH:34][C:35]([O:37][C:38]3[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=3)=[CH:36][C:31]=2[F:30])=[O:49])[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 536301804-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzenesulfonamideHCID 595579602-Fluoro-4-(2-methylpyridin-4-yloxy)phenylamine

Product 1

HCID 115783564-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenyl]ureido}pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzene-sulfonamideYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzenesulfonamide (150 mg, 0.36 mmol) in anhydrous DCE (1 mL) was added CDT (64 mg, 0.39 mmol, 1.1 eq), and the reaction was stirred under nitrogen at 50° C. for 18 h. A solution of 2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenylamine (86 mg, 0.39 mmol, 1.1 eq) in anhydrous THF (1 mL) was added to the reaction, and the solution was stirred under at 50° C. for 3 days. The reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The crude product was purified by HPLC and recrystallized from DCM/hexane to give 55 mg (23%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 8.92 (d, J=14.4 Hz, 2H), 8.30 (d, J=5.7 Hz, 1H), 8.07 (t, J=9 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.68 (t, J=6 Hz, 1H), 7.58 to 7.51 (m, 2H), 7.25 (dd, J=11.4, 2.4 Hz, 1H), 6.97 to 6.92 (m, 1H), 6.77 (d, J=2.4 Hz, 1H), 6.74 to 6.70 (m, 1H), 6.41 (s, 1H), 3.45 (t, J=4.5 Hz, 4H), 2.93 (q, J=6H, 2H), 2.65 (s, 3H), 2.39 (s, 3H), 2.25 (t, J=6.9 Hz, 2H), 2.20 to 2.17 (m, 4H), 1.27 (s, 9H); MS LC-MS [M+H]+=666, RT=2.26 min.

Workup

  1. stirringthe solution was stirred under at 50° C. for 3 days
  2. customThe reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated at reduced pressure
  6. customThe crude product was purified by HPLC
  7. customrecrystallized from DCM/hexane

Sources & evidence

ORD record
ord-030e415ee3af482588021c538a101994
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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