Potassium Carbonate → VPS34 inhibitor 1

HRID 2359754Notes

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+].[OH:31][C:32]([CH3:39])([CH3:38])[CH2:33][NH:34][C:35]([NH2:37])=[NH:36]>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:37]=[C:35]([NH:34][CH2:33][C:32]([CH3:39])([OH:31])[CH3:38])[N:36]=2)[CH2:3][CH2:2]1

Participants

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) (50 mg, 0.155 mmol) in DMF (1288 μl), 1-(2-hydroxy-2-methylpropyl)guanidine and potassium carbonate (107 mg, 0.773 mmol) were added and the reaction mixture was stirred at 120° C. for 2 hours. The crude product was purified by reverse-phase HPLC [30-90% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product (23.8 mg, 39%).

Workup

customThe crude product was purified by reverse-phase HPLC [30-90% organic phase over 15 minutes]

Sources & evidence

ORD record: ord-f0ec879d5d474fce90e5876d078fdc10
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08685993B2

Reaction notes

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