Potassium Carbonate → HCID 58169313, compound

HRID 1484951Notes

Reaction equation

HRID 1484951 reaction equation
[C:1]([O:4][CH2:5][CH2:6][C:7]1[C:8]([NH:14][C:15]2[CH:19]=[C:18]([CH:20]3[CH2:22][CH2:21]3)[NH:17][N:16]=2)=[N:9][C:10](Br)=[N:11][CH:12]=1)(=[O:3])[CH3:2].[C:23]([NH:27][S:28]([C:31]1[S:32][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:35]=1)(=[O:30])=[O:29])([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+].O1CCOCC1>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].O>[C:1]([O:4][CH2:5][CH2:6][C:7]1[C:8]([NH:14][C:15]2[CH:19]=[C:18]([CH:20]3[CH2:22][CH2:21]3)[NH:17][N:16]=2)=[N:9][C:10]([C:33]2[S:32][C:31]([S:28](=[O:30])(=[O:29])[NH:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[CH:35][CH:34]=2)=[N:11][CH:12]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 57468817N-tert-butyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamideHCID 58169319HCID 58169319, compound

Product 1

HCID 58169313HCID 58169313, compoundYield 60%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(2-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-5-yl)ethyl acetate (366 mg, 1.0 mmol, 1.0 eq), N-tert-butyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide (517 mg, 1.5 mmol, 1.5 eq), PdCl2(dppf) (81.6 mg, 0.1 mmol, 0.1 eq), K2CO3 (417 mg, 3.0 mmol, 3.0 eq), dioxane (15 mL) and water (2 mL) was heated for 1 h at 90° C. under nitrogen atmosphere. The solvent was removed and the residue was purified by silica gel chromatography (PE/EtOAc=1:1) to yield 2-(2-(5-(N-tert-butylsulfamoyl)thiophen-2-yl)-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-5-yl)ethyl acetate (300 mg, 60%). LC-MS (m/z)=505.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ 0.73-0.74 (m, 2H), 0.96-0.97 (m, 2H), 1.16 (s, 9H), 1.90-1.94 (m, 1H), 1.97 (s, 3H), 2.96 (t, J=5.6 Hz, 2H), 4.17 (d, J=5.6 Hz, 2H), 6.47 (s, 1H), 7.58 (d, J=4.0 Hz, 1H), 7.72 (d, J=4.0 Hz, 1H), 7.87 (s, 1H), 8.13 (s, 1H), 9.37 (s, 1H), 12.19 (s, 1H)

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by silica gel chromatography (PE/EtOAc=1:1)

Sources & evidence

ORD record
ord-1376df2b03104f948f37878882c7656a
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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