Sodium Carbonate → 4-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

HRID 1039904Notes

Reaction equation

HRID 1039904 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[CH:16]=[C:15](B4OC(C)(C)C(C)(C)O4)[CH:14]=[C:13]([CH3:26])[CH:12]=3)[N:5]=2)[CH2:3][CH2:2]1.Br[C:28]1[S:32][CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC1CCCO1.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].C(Cl)Cl>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[CH:16]=[C:15]([C:28]4[S:32][CH:31]=[N:30][CH:29]=4)[CH:14]=[C:13]([CH3:26])[CH:12]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5460595-BromothiazoleHCID 672563904-cyclopropyl-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine

Product 1

HCID 584561394-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineYield 91.1%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-cyclopropyl-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (750 mg, 2.14 mmol) in 2-methyl tetrahydrofuran (10.7 mL) were added 5-bromothiazole (406 mg, 2.35 mmol), PdCl2(dppf)-CH2Cl2 (87 mg, 0.11 mmol), and aqueous sodium carbonate (2 M, 2.14 mL). The reaction was sealed and purged with N2 for 5 minutes. The reaction was stirred at 80° C. for 16 h and cooled to room temperature. Water was added and extracted with EtOAc (3×). The combined organic layers were dried (magnesium sulfate), concentrated, and purified by flash chromatography to afford 4-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (600 mg, 1.95 mmol, 91% yield) as an off-white solid. MS ESI: [M+H]+ m/z 309.1. 1H NMR (500 MHz, DMSO-d6) δ 9.49 (s, 1H), 9.06 (s, 1H), 8.26 (d, 5.0, 1H), 8.19 (s, 1H), 8.04 (s, 1H), 7.43 (s, 1H), 7.10 (s, 1H), 6.82 (d, J=5.0, 1H), 2.29 (s, 3H), 2.00 (m, 1H), 1.17-0.93 (m, 4H).

Workup

  1. customThe reaction was sealed
  2. custompurged with N2 for 5 minutes
  3. temperaturecooled to room temperature
  4. additionWater was added
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic layers were dried (magnesium sulfate)
  7. concentrationconcentrated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-da30e1c6437542ceb0162ca6cdcf8d06
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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