3-Butyn-1-OL → 4-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)but-3-yn-1-ol

HRID 578752Notes

Reaction equation

HRID 578752 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]([NH2:11])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.N1CCCC1.[CH2:17]([OH:21])[CH2:18][C:19]#[CH:20]>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[NH4+]>[NH2:11][C:6]1[C:5]2=[CH:4][CH:3]=[C:2]([C:20]#[C:19][CH2:18][CH2:17][OH:21])[N:10]2[N:9]=[CH:8][N:7]=1

Participants

7

Reactant 3

HCID 135663-Butyn-1-OLHCID 31268PyrrolidineHCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 585295674-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)but-3-yn-1-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
85 °C

Procedure

7-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (1.0 g, 4.69 mmol), copper(I) iodide (89 mg, 0.47 mmol, 0.1 eq.) and tetrakis(triphenylphosphine)palladium(0) (542 mg, 0.47 mmol, 0.1 eq.) were charged into a microwave reactor vial and evacuated for 1 h. The vessel was then vented with argon, pyrrolidine (15 mL) and 3-butyn-1-ol (3.36 g, 47 mmol, 10 eq.) were added, and the vessel was crimp-capped and heated to 85° C. for 120 min in a single-mode microwave device. After cooling, the reaction mixture was poured into 120 mL of concentrated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and evaporated, and the residue was purified by flash chromatography (Biotage silica column, ethyl acetate). The resulting product (735 mg) was sufficiently pure (66% by HPLC) for further transformations.

Workup

  1. customevacuated for 1 h
  2. additionwere added
  3. customthe vessel was crimp-capped
  4. temperatureAfter cooling
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. customevaporated
  8. customthe residue was purified by flash chromatography (Biotage silica column, ethyl acetate)

Sources & evidence

ORD record
ord-ffd49be93791436989cec50e048dfc1b
Source dataset
uspto-grants-2015_05
Patent number
US09040691B2

Reaction notes

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