Dichloromethane → 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-tert-butylthiophene-2-sulfonamide

HRID 1484934

Reaction equation

C(Cl)Cl.[C:4]([NH:8][S:9]([C:12]1[S:16][C:15](B(O)O)=[CH:14][CH:13]=1)(=[O:11])=[O:10])([CH3:7])([CH3:6])[CH3:5].Br[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:32]=[C:31]([CH:33]3[CH2:35][CH2:34]3)[NH:30][N:29]=2)[C:24]([Br:36])=[CH:23][N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>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]>[Br:36][C:24]1[C:25]([NH:27][C:28]2[CH:32]=[C:31]([CH:33]3[CH2:35][CH2:34]3)[NH:30][N:29]=2)=[N:26][C:21]([C:15]2[S:16][C:12]([S:9]([NH:8][C:4]([CH3:7])([CH3:6])[CH3:5])(=[O:11])=[O:10])=[CH:13][CH:14]=2)=[N:22][CH:23]=1

Participants

Conditions

Temperature: 90 °C

Procedure

The mixture of Pd(dppf)Cl2.CH2Cl2 (457 mg, 0.56 mmol, 0.1 eq), 5-(N-tert-butylsulfamoyl)thiophen-2-ylboronic acid (2.95 g, 11.2 mmol, 2.0 eq), 2,5-dibromo-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (2 g, 5.6 mmol, 1.0 eq) and saturate Na2CO3 (5 mL) in dioxane (30 mL) was heated to 90° C. for 1 h under nitrogen atmosphere. The reaction mixture was cooled to room temperature, and extracted with THF. The combined layers were evaporated and residue purified by silica gel chromatography (EtOAc/Petroleum ether from 10:1 to 2:1) to afford compound 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-tert-butylthiophene-2-sulfonamide (1.6 g, 59%). LC-MS (m/z)=497 [M+H]+.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with THF
customThe combined layers were evaporated
customresidue purified by silica gel chromatography (EtOAc/Petroleum ether from 10:1 to 2:1)

Sources & evidence

ORD record: ord-b20faa5a594b40e8917119230c1bbaf4
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Linked notes

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