Diisopropylethylamine → N-(6-([1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

HRID 1925102Notes

Reaction equation

I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[N:17]1[N:18]=[C:19]([SH:26])[N:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=12.CCN(C(C)C)C(C)C>COCCOC.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].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[N:17]1[N:18]=[C:19]([S:26][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]4[CH2:16][CH2:15]4)=[O:13])[N:10]=3)[N:7]=2)[N:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=12

Participants

Conditions

Temperature: 120 °C

Procedure

N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (0.5 g, 1.52 mmol), [1,2,4]triazolo[4,3-a]pyridine-3-thiol (0.23 g, 1.52 mmol), Tris(dibenzylideneacetone)dipalladium(0) (84 mg, 0.09 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (106 mg g, 0.18 mmol), and DIEA (0.531 mL, 3.05 mmol) were dissolved in DME (15.2 mL) and heated in a microwave at 120° C. for 30 min. The reaction mixture was concentrated to dryness, reconstituted in DMSO, and purified by preparative LCMS to give N-(6-([1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (1 g, 43%) as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ=11.17 (s, 1 H), 8.57-8.44 (m, 1 H), 8.03-7.94 (m, 1 H), 7.96-7.88 (m, 2 H), 7.59 (ddd, J=1.0, 6.6, 9.3 Hz, 1 H), 7.22-7.11 (m, 1 H), 7.11-7.03 (m, 1 H), 1.97-1.84 (m, 1 H), 0.83-0.73 (m, 4 H) ESI-MS:m/z 352.3 (M+H)+. MP 193-195° C.

Workup

concentrationThe reaction mixture was concentrated to dryness
custompurified by preparative LCMS

Sources & evidence

ORD record: ord-85e6e090128f45dc9280217777b6d3af
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178534B2

Reaction notes

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