Potassium Carbonate → 4'-(Cyclopropylmethyl)-2'-(methylsulfanyl)-N-pyridin-4-yl-4,5'-bipyrimidin-2-amine

HRID 1397158Notes

Reaction equation

HRID 1397158 reaction equation
[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:12]=2)=[CH:7]\N(C)C)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].S(O)(O)(=O)=O.[CH3:36][S:37][C:38](=[NH:40])[NH2:39]>CN(C=O)C>[CH:1]1([CH2:4][C:5]2[C:6]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[N:12]=3)=[CH:7][N:39]=[C:38]([S:37][CH3:36])[N:40]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 752702-Methyl-2-thiopseudourea sulfateHCID 67983720(3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-one

Product 1

HCID 679838584'-(Cyclopropylmethyl)-2'-(methylsulfanyl)-N-pyridin-4-yl-4,5'-bipyrimidin-2-amineYield 3.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (Z)-1-cyclopropyl-4-(dimethylamino)-3-(2-(pyridin-4-ylamino)pyrimidin-4-yl)but-3-en-2-one (9) (200 mg, 0.618 mmol) in DMF (5.154 ml) was added potassium carbonate (256 mg, 1.855 mmol) and 2-methyl-2-thiopseudourea sulfate (129 mg, 0.928 mmol). The reaction was warmed to 120° C. and stirred for 1 hr. The solvent was evaporated and the crude residue partitioned between DCM and water. The organic layer was washed with brine, dried with sodium sulfate, and concentrated. The crude product was purified by flash chromatography with a gradient of 2-10% MeOH in DCM and further purified reverse phase HPLC with a gradient of 10-100% MeCN in H2O to give 7.8 mg of the desired product as a white solid. HRMS (ES+)=351.1391. UV-LC: 100/100% UV purity at 214/254 nm; HPLC: tR=3.38 minute over 7.75 minutes. 1H NMR (400 MHz, MeOD) δ ppm 0.10-0.14 (m, 2 H) 0.41-0.47 (m, 2 H) 1.03-1.15 (m, 1 H) 2.63 (s, 3 H) 2.94 (d, J=7.07 Hz, 2 H) 7.18 (d, J=5.56 Hz, 1 H) 7.83 (d, J=7.07 Hz, 2 H) 8.31 (d, J=7.07 Hz, 2 H) 8.64 (s, 1 H) 8.65 (d, J=5.05 Hz, 1 H)

Workup

  1. customThe solvent was evaporated
  2. customthe crude residue partitioned between DCM and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography with a gradient of 2-10% MeOH in DCM and further purified reverse phase HPLC with a gradient of 10-100% MeCN in H2O

Sources & evidence

ORD record
ord-29ba0f4e562f4f3ebc9e70257af9f883
Source dataset
uspto-grants-2014_12
Patent number
US08901147B2

Reaction notes

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