Dimethylformamide → 2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-4-(methylamino)pyrimidine-5-carbonitrile

HRID 2409099Notes

Reaction equation

Br[C:2]1[C:3]([NH:16][CH3:17])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:15])[C:13]=2[CH3:14])=[N:6][CH:7]=1.[CH3:18][N:19](C=O)C>[C-]#N.[Zn+2].[C-]#N.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].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.[Fe+2]>[CH3:15][N:12]1[C:13]([CH3:14])=[C:9]([NH:8][C:5]2[N:4]=[C:3]([NH:16][CH3:17])[C:2]([C:18]#[N:19])=[CH:7][N:6]=2)[CH:10]=[N:11]1

Participants

Conditions

Temperature: 105 °C

Procedure

To a mixture of 5-bromo-N2-(1,5-dimethyl-1H-pyrazol-4-yl)-N4-methylpyrimidine-2,4-diamine (95 mg, 0.32 mmol), zinc cyanide (70 mg, 0.60 mmol), Pd2(dba)3 (11 mg, 0.012 mmol), DPPF (13 mg, 0.023 mmol) was added DMF (3.5 mL). The reaction was then heated in a sealed tube at 105° C. for 18 h. The reaction mixture was filtered and concentrated. The crude product was purified by reverse phase HPLC to give 2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-4-(methylamino)pyrimidine-5-carbonitrile (19 mg, 25%). LCMS (Method A): [MH+]=244.1 at 2.53 min. 1H-NMR (DMSO): δ 8.96 (m, 1H), 8.21 (m, 1H), 7.49 (m, 2H), 3.69 (s, 3H), 2.84 (m, 3H), 2.14 (m, 3H). K1=0.025.

Workup

filtrationThe reaction mixture was filtered
concentrationconcentrated
customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-2f32becfc4ba46c2be66b15cd07c4a73
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815882B2

Reaction notes

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