Sodium Carbonate → HCID 50943451, compound

HRID 1484875Notes

Reaction equation

HRID 1484875 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]([F:17])=[CH:4][N:3]=1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1B(O)O.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].O>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([NH:8][C:6]3[C:5]([F:17])=[CH:4][N:3]=[C:2]([C:19]4[S:18][CH:22]=[CH:21][CH:20]=4)[N:7]=3)[CH:13]=2)[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27339602-Thiopheneboronic acidHCID 58169400HCID 58169400, compound

Product 1

HCID 50943451HCID 50943451, compoundYield 28.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoropyrimidin-4-amine (250 mg, 0.84 mmol, 1.0 eq), thiophen-2-ylboronic acid (150 mg, 1.18 mmol, 1.4 eq), Pd(dppf)Cl2 (69 mg, 0.084 mmol, 0.1 eq), Na2CO3 (356 mg, 3.36 mmol, 4 eq), 1,4-dioxane (10 ml) and water (1.5 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 100:1 as eluent) to afford title compound N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-2-(thiophen-2-yl)pyrimidin-4-amine (Compound 41) (71.2 mg, 28.1%) as a solid. LC-MS (m/z)=302.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ 0.77 (d, J=4 Hz, 2H), 1.01 (d, J=7.2 Hz, 2H), 1.97 (t, J=4.4 Hz, 1H), 6.58 (s, 1H), 7.21 (t, J=4.2 Hz, 1H), 7.76 (m, 2H), 8.32 (d, J=3.2 Hz, 1H), 10.12 (s, 1H), 12.24 (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 100:1 as eluent)

Sources & evidence

ORD record
ord-f1f8bac22b4243a4bd495c23ffb6bcf7
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

Loading…