Sodium Carbonate → 5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-methoxyethyl)thiophene-2-sulfonamide

HRID 1484882Notes

Reaction equation

HRID 1484882 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([Cl:17])=[CH:4][N:3]=1.[CH3:18][O:19][CH2:20][CH2:21][NH:22][S:23]([C:26]1[S:27][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:30]=1)(=[O:25])=[O:24].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:17][C:5]1[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)=[N:7][C:2]([C:28]2[S:27][C:26]([S:23]([NH:22][CH2:21][CH2:20][O:19][CH3:18])(=[O:24])=[O:25])=[CH:30][CH:29]=2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 581691502-bromo-5-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amineHCID 58169206N-(2-methoxyethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide

Product 1

HCID 581692875-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-methoxyethyl)thiophene-2-sulfonamideYield 28.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-5-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (250 mg, 0.795 mmol), N-(2-methoxyethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide (359 mg, 1.034 mmol, 1.3 eq), Pd(dppf)Cl2 (65 mg, 0.0795 mmol, 0.1 eq) and Na2CO3 (295 mg, 2.783 mmol, 3.5 eq) in 1,4-dioxane (5 mL) and water (1 mL) was stirred at 100° C. under a nitrogen atmosphere for 15 h. The reaction mixture was allowed to cool to room temperature and concentrated to give a residue. The residue was purified by silica gel chromatography (CH2Cl2/methanol 500:1 to 50:1 as eluent) to afford title compound 5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-methoxyethyl) thiophene-2-sulfonamide (Compound 88) (71.2 mg, 28.1%) as solid. LC-MS (m/z)=455.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ 0.75 (d, J=3.6 Hz, 2H), 0.99 (d, J=6.4 Hz, 2H), 1.94 (s, 1H), 3.04 (t, J=5.2 Hz, 2H), 3.20 (s, 3H), 3.37 (t, J=5.0 Hz, 2H), 6.39 (s, 1H), 7.61 (d, J=3.2 Hz, 1H), 7.77 (d, J=3.6 Hz, 1H), 8.15 (s, 1H), 8.46 (s, 1H), 9.49 (s, 1H), 12.35 (s, 1H).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated
  3. customto give a residue
  4. customThe residue was purified by silica gel chromatography (CH2Cl2/methanol 500:1 to 50:1 as eluent)

Sources & evidence

ORD record
ord-bb3c6b39e005464fb737102a9c78504e
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

Loading…