Diisopropylethylamine → Tert-butyl 6-(6-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-ylcarbamate

HRID 1925111Notes

Reaction equation

HRID 1925111 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[N:10]=2)[N:7]=1.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([SH:29])=[N:27][N:28]=2)[CH:25]=1.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.CCN(C(C)C)C(C)C>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].COCCOC>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([S:29][C:2]3[CH:3]=[CH:4][C:5]4[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[N:10]=4)[N:7]=3)=[N:27][N:28]=2)[CH:25]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 46941915Tert-butyl (6-iodoimidazo[1,2-b]pyridazin-2-yl)carbamateHCID 178527923HCID 178527923, compound

Product 1

HCID 67520113Tert-butyl 6-(6-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-ylcarbamateYield 102.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

Combined compound 7B (50 mg, 0.14 mmol), 6-chloro-[1,2,4]triazolo[4,3-a]pyridine-3-thiol (28 mg, 0.15 mmol), Tris(dibenzylideneacetone)dipalladium(0) (11 mg, 0.01 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (14 mg, 0.025 mmol), DIEA (48 uL, 0.28 mmol) and DME (1.4 mL) and heated in a microwave unit at high absorbance, 120° C. for 30 min. The resulting crude material was purified by silica gel using 5% MeOH in DCM. The cleanest fractions were concentrated to give compound 7 (0.06 g; quantitative yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.18 (br. s., 1 H), 8.86-8.82 (m, 1 H), 8.11-8.05 (m, 1 H), 7.89 (d, J=9.3 Hz, 1 H), 7.73 (s, 1 H), 7.66 (dd, J=1.9, 9.7 Hz, 1 H), 7.09 (d, J=9.6 Hz, 1 H), 1.48-1.41 (m, 9 H), ESI-MS:m/z 418.2.0 (M+H)+.

Workup

  1. customThe resulting crude material was purified by silica gel using 5% MeOH in DCM
  2. concentrationThe cleanest fractions were concentrated

Sources & evidence

ORD record
ord-e0ff7d11d6a742d193d66e023b5c8426
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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