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

HRID 1972775Notes

Reaction equation

HRID 1972775 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.[CH2:12]([OH:16])[CH2:13][C:14]#[CH:15].[Cl-].[NH4+]>N1CCCC1.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.[Cu]I>[NH2:11][C:6]1[C:5]2=[CH:4][CH:3]=[C:2]([C:15]#[C:14][CH2:13][CH2:12][OH:16])[N:10]2[N:9]=[CH:8][N:7]=1

Participants

7

Reactant 3

HCID 135663-Butyn-1-OLHCID 25517Ammonium ChlorideHCID 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-olYield 61%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 31268PyrrolidineSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (2.25 g, 10.6 mmol), tetrakis(triphenylphosphine)palladium(0) (610 mg, 0.53 mmol), and copper(I) iodide (500 mg, 2.64 mmol) in degassed pyrrolidine (45 mL) was added 3-butyn-1-ol (1.6 mL, 21.1 mmol), dropwise. The reaction was heated (50° C.) for 17 h. After cooling to rt, saturated aqueous ammonium chloride solution was added (50 mL) and the mixture was extracted first with ethyl acetate (4×50 mL) then with 3:1 chloroform/isopropanol (5×100 mL). The organics were separately dried (Na2SO4) and the solvent was evaporated. The combined crude oils were purified via flash chromatography on silica gel eluting with 100% ethyl acetate, followed by trituration with ethyl acetate to obtain 1.3 g (61%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.85 (s, 1 H), 7.81 (br s, 2 H), 6.82 (d, 1 H), 6.75 (s, 1 H), 4.91 (t, 1 H), 3.58 (q, 2 H), 2.63 (t, 2 H); ES-MS m/z 203.2 [M+H]+, HPLC RT (min) 1.05.

Workup

  1. temperatureAfter cooling to rt
  2. extractionthe mixture was extracted first with ethyl acetate (4×50 mL)
  3. dry with materialThe organics were separately dried (Na2SO4)
  4. customthe solvent was evaporated
  5. customThe combined crude oils were purified via flash chromatography on silica gel eluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-2e432e128fc54a1cb74325db8734802f
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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