Potassium Phosphate, Tribasic → N2-{2-Isopropoxy-4-methyl-5-[1-(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-phenyl}-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine

HRID 386776Notes

Reaction equation

HRID 386776 reaction equation
Br[C:2]1[C:3]([CH3:33])=[CH:4][C:5]([O:29][CH:30]([CH3:32])[CH3:31])=[C:6]([NH:8][C:9]2[N:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[C:12]([CH3:28])=[CH:11][N:10]=2)[CH:7]=1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[N:44][N:45]([CH2:47][CH2:48][N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:46]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.O.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]>[CH:30]([O:29][C:5]1[CH:4]=[C:3]([CH3:33])[C:2]([C:42]2[CH:43]=[N:44][N:45]([CH2:47][CH2:48][N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:46]=2)=[CH:7][C:6]=1[NH:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[C:12]([CH3:28])=[CH:11][N:10]=1)([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 59764523N2-(5-Bromo-2-isopropoxy-4-methyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]pyrimidine-2,4-diamine

Product 1

HCID 59764556N2-{2-Isopropoxy-4-methyl-5-[1-(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-phenyl}-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

A mixture of N2-(5-Bromo-2-isopropoxy-4-methyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine from the previous step (53 mg, 0.099 mmol), 4-{2-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-ethyl}-morpholine (Boron Molecular, 61 mg 0.20 mmol), K3PO4 (58 mg), Pd2(dba)3 (10 mg), and tricyclohexylphosphine (8 mg) in 1 mL of 1,4-dioxane/H2O (3/1 v/v) is heated in a sealed tube at 150° C. for 20 min under microwave radiation. The reaction mixture is filtered through a small plug of Celite and concentrated. Final purification using preparative RP LC-MS affords N2-{2-Isopropoxy-4-methyl-5-[1-(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-phenyl}-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine (37). MS (ES+): 634.3 (MH+).

Workup

  1. filtrationThe reaction mixture is filtered through a small plug of Celite
  2. concentrationconcentrated
  3. customFinal purification

Sources & evidence

ORD record
ord-690396cf19514419b0d7eba2be2db026
Source dataset
uspto-grants-2013_02
Patent number
US08372858B2

Reaction notes

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