Cesium carbonate → HCID 57635866, compound

HRID 2109947Notes

Reaction equation

HRID 2109947 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=2[CH3:18])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:20]1[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:24][N:23]=[C:22]([S:31][CH3:32])[N:21]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:24]2[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:20][N:21]=[C:22]([S:31][CH3:32])[N:23]=2)[N:7]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=2[CH3:18])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 634876Binap, (A+-)-HCID 16769190HCID 16769190, compound

Product 1

HCID 57635866HCID 57635866, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

To a dried 15 mL tube was added 3-tert-butyl-1-(2,5-dimethylphenyl)-1H-pyrazol-5-amine (106 mg, 0.44 mmol), synthesized in the same manner as intermediate F, ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (101 mg, 0.44 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), BINAP (27 mg, 0.044 mmol), and Cs2CO3 (199 mg, 0.61 mmol). The flask was degassed followed by addition of toluene (2 mL), and the mixture was then heated to 110° C. for 20 h. The mixture was cooled to rt, filtered through a silica gel plug using ethyl acetate as eluent, concentrated to dryness, and subjected to HPLC purification using a gradient elution from 45% to 90% acetonitrile in water to afford 81 mg (42%) of the desired product. 1H NMR (300 MHz, CD2Cl2) δ 10.23 (s, 1H), 8.72 (s, 1H), 7.24 (dd, 2H), 7.16 (s, 1H), 6.78 (s, 1H), 4.20 (q, 2H), 2.64 (s, 3H), 2.38 (s, 3H), 2.04 (s, 3H), 1.34 (s, 9H), 1.28 (t, 3H);. ES-MS m/z 440.2 (MH+); HPLC RT (min) 4.66.

Workup

  1. customThe flask was degassed
  2. additionfollowed by addition of toluene (2 mL)
  3. temperatureThe mixture was cooled to rt
  4. filtrationfiltered through a silica gel plug
  5. concentrationconcentrated to dryness
  6. customsubjected to HPLC purification
  7. washa gradient elution from 45% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-e8cbf29df4624b04af2bae56e6336ab9
Source dataset
uspto-grants-2009_04
Patent number
US07517878B2

Reaction notes

Loading…