Triethylamine → Tert-butyl(6-(2-(triethylsilyl)ethynyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

HRID 1513665

Reaction equation

HRID 1513665 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N:9][N:10]=2)[N:7]=1.[CH2:20]([Si:22]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:23]#[CH:24])[CH3:21].C(N(CC)CC)C>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.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.[Cu](I)I.C(#N)C>[C:15]([O:14][C:13](=[O:19])[NH:12][CH2:11][C:8]1[N:6]2[N:7]=[C:2]([C:21]#[C:20][Si:22]([CH2:27][CH3:28])([CH2:25][CH3:26])[CH2:23][CH3:24])[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 637947(Triethylsilyl)acetyleneHCID 57691389tert-Butyl ((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate

Product 1

HCID 57691160Tert-butyl(6-(2-(triethylsilyl)ethynyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A 1 L-round-bottomed flask flushed with argon was charged with tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (12.00 g, 42.3 mmol), Pd(dppf)Cl2—CH2Cl2 adduct (3.45 g, 4.23 mmol), copper iodide (2.01 g, 10.6 mmol) at room temperature. Acetonitrile (400 mL) was added followed by triethyl(ethynyl)silane (37.9 ml, 211 mmol). Upon stirring the reaction mixture turned dark red. Triethylamine (177 ml, 1269 mmol) was added via cannula over five minutes. The first drops resulted in a change of color to light yellow/orange. At the end of the addition, the reaction mixture was dark red again. After stirring at 50° C. for one hour, the mixture was cooled to room temperature and concentrated in vacuo. Purification by MPLC (ISCO, EtOAc/MeOH: 100/0 to 90/10) afforded the desired product. The material was taken forward without further purification. MS m/z=388.3 [M+1]+. Calc'd for C19H29N5O2Si: 387.2.

Workup

  1. customA 1 L-round-bottomed flask flushed with argon
  2. customThe first drops resulted in a change of color to light yellow/orange
  3. additionAt the end of the addition
  4. stirringAfter stirring at 50° C. for one hour
  5. concentrationconcentrated in vacuo
  6. customPurification by MPLC (ISCO, EtOAc/MeOH: 100/0 to 90/10)

Sources & evidence

ORD record
ord-8ef30de51c334458bdd4c07204ffd6a7
Source dataset
uspto-grants-2012_07
Patent number
US08217177B2

Linked notes

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