Diisopropylethylamine → (5-Butyl-1-(5-methyl-4-(thiophen-2-yl)pyrimidin-2-yl)-1H-pyrazol-4-yl)(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone

HRID 910259Notes

Reaction equation

HRID 910259 reaction equation
[CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:20]C=N[CH:17]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[C:22](O)=[O:23])[CH2:2][CH2:3][CH3:4].[N:25]1[N:26]=[CH:27][N:28]2[CH2:33][CH2:32][NH:31][CH2:30][C:29]=12.CN(C(ON1N=N[C:44]2C=CC=C[C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:20][CH:43]=[CH:44][CH:17]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[C:22]([N:31]1[CH2:32][CH2:33][N:28]2[CH:27]=[N:26][N:25]=[C:29]2[CH2:30]1)=[O:23])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 179987185H,6H,7H,8H-(1,2,4)triazolo(4,3-a)pyrazineHCID 60207815HCID 60207815, compound

Product 1

HCID 67390453(5-Butyl-1-(5-methyl-4-(thiophen-2-yl)pyrimidin-2-yl)-1H-pyrazol-4-yl)(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanoneYield 3.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-butyl-1-(5-methyl-4-(thiazol-5-yl)pyrimidin-2-yl)-1H-pyrazole-4-carboxylic acid (72 mg, 0.21 mmol), 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (50 mg, 0.23 mmol), HBTU (119 mg, 0.32 mmol) and 4 mL of DMF was added DIEA (54 μL, 0.73 mmol). The reaction was stirred at room temperature for 2 hours at which time the crude mixture was purified directly by reverse phase preparative HPLC to provide 3.0 mg of 30 as a white solid. 1H NMR (400 MHz, MeOD-d3) δ 0.78 (t, J=7.2 Hz, 3H), 1.35 (m, 2H), 1.61 (m, 2 H), 2.69 (s, 3H), 3.4 (t, J=7.7 Hz, 2H), 4.18 (t, J=5.1 Hz, 2H), 4.31 (t, J=5.5 Hz, 2H), 5.10 (s, 2H), 7.32 (t, J=4.5 Hz, 1H), 7.82 (d, J=5.1 Hz, 1H), 7.96 (s, 1H), 7.99 (d, J=2.7 Hz, 1H), 8.54 (s, 1H), 8.76 (s, 1H). LCMS (ES+) m/z 449 (M+1).

Workup

  1. customwas purified directly by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-457f18792aa04102aa5d4f06cd645031
Source dataset
uspto-grants-2011_09
Patent number
US08022061B2

Reaction notes

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