Potassium Carbonate → HCID 68751488, compound

HRID 1038839

Reaction equation

HRID 1038839 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][CH:12]2[CH2:14][CH2:13]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:15][S:16]([C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>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].CC(O)(C)C>[CH2:12]([NH:11][C:4]1[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=[C:2]([NH:23][C:22]2[CH:21]=[CH:20][C:19]([S:16]([CH3:15])(=[O:18])=[O:17])=[CH:25][CH:24]=2)[N:3]=1)[CH:14]=[CH2:13]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 796174-(Methylsulfonyl)anilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866650932-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

Product 1

HCID 68751488HCID 68751488, compoundYield 27.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.09 g, 0.429 mmol, Preparation #A.1), 4-(methylsulfonyl)aniline (0.077 g, 0.451 mmol, Oakwood), X-Phos (0.020 g, 0.043 mmol), Pd2dba3 (0.020 g, 0.021 mmol), K2CO3 (0.062 g, 0.451 mmol) and t-BuOH (3.5 mL). The vial was purged with argon and heated at about 100° C. overnight. The mixture was diluted with CHCl3 (about 10 mL) passed through a SiCO3 SPE cartridge and concentrated. The crude product was purified by preparative reverse phase HPLC (Table 2, Method a) to provide N4-allyl-N2-(4-(methylsulfonyl)phenyl)furo[3,2-d]pyrimidine-2,4-diamine (0.041 g, 27%): 1H NMR (DMSO-d6) δ 9.53 (s, 1H), 8.11 (d, J=2.1 Hz, 1H), 8.02 (m, 3H), 7.72 (d, J=8.9 Hz, 2H), 6.80 (d, J=2.1 Hz, 1H), 6.00 (ddd, J=17.1, 10.2, 5.1 Hz, 1H), 5.22 (dd, J=17.1, 1.6 Hz, 1H), 5.11 (dd, J=10.5, 1.6 Hz, 1H), 4.14 (dd, J=5.1 Hz, 2H), 3.11 (s, 3H). Syk IC50=B.

Workup

  1. customThe vial was purged with argon
  2. additionThe mixture was diluted with CHCl3 (about 10 mL)
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative reverse phase HPLC (Table 2, Method a)

Sources & evidence

ORD record
ord-073ca5a0a38f4c1599ce3e0d5c1fe0e7
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Linked notes

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