Triethylamine → (S)-6-(4-hydroxypiperidin-1-yl)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)pyridazine-3-carboxamide

HRID 1755233Notes

Reaction equation

HRID 1755233 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[N:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[N:17]1[CH:18]=[CH:19][N:20]2[CH:25]=[CH:24][N:23]=[C:22]([N:26]3[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]3)[C:21]=12.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CS(C)=O>[OH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]2[N:13]=[N:12][C:11]([C:14]([NH:31][C@H:28]3[CH2:29][CH2:30][N:26]([C:22]4[C:21]5[N:20]([CH:19]=[CH:18][N:17]=5)[CH:25]=[CH:24][N:23]=4)[CH2:27]3)=[O:16])=[CH:10][CH:9]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 607922556-(4-Hydroxypiperidin-1-yl)pyridazine-3-carboxylic acidHCID 75204084HCID 75204084, compound

Product 1

HCID 75204086(S)-6-(4-hydroxypiperidin-1-yl)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)pyridazine-3-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylic acid (0.10 g, 0.45 mmol, 1 eq) and (S)-1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-amine (0.12 g, 0.44 mmol, 1 eq) in 1 mL of DMSO was added triethylamine (0.19 mL, 0.49 mmol, 1.1 eq) and HATU (0.19 g, 0.49 mmol, 3 eq). The mixture was stirred at room temperature for 30 min then concentrated and purified by HPLC to afford (S)-6-(4-hydroxypiperidin-1-yl)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)pyridazine-3-carboxamide (0.12 g, 0.29 mmol, 66%). 1H NMR (400 MHz, CD3OD) δ 8.05 (s, 1 H), 8.02 (d, J=9.8 Hz, 1 H), 7.94 (d, J=5.5 Hz, 1 H), 7.81 (s, 1 H), 7.5 (d, J=9.8 Hz, 1 H), 7.18 (d, J=5.8 Hz, 1 H), 4.98-4.80 (m, 1 H), 4.80-3.80 (br, 4 H), 4.20-4.10 (m, 2 H), 4.00-3.90 (m, 1 H), 3.55-3.45 (m, 2 H), 2.60-2.35 (m, 2 H), 2.05-1.95 (m, 2 H), 1.68-1.55 (m, 2 H); MS: (ES) m/z calculated for C20H24N8O2 [M+H]+ 409.2, found 409.

Workup

  1. concentrationthen concentrated
  2. custompurified by HPLC

Sources & evidence

ORD record
ord-d30ef66105474ac3bcc863c2f6848cf2
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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