Ethyl Acetate → HCID 58529276, compound

HRID 1972792Notes

Reaction equation

HRID 1972792 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:15]3[CH:16]=[CH:17][C:18]4[C:22]([CH:23]=3)=[N:21][N:20]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:19]=4)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13]O)[N:6]2[N:5]=[CH:4][N:3]=1.C(Br)(Br)(Br)[Br:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(C)=O>C1COCC1>[CH2:24]([N:20]1[CH:19]=[C:18]2[C:22]([CH:23]=[C:15]([C:8]3[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][Br:32])[N:6]4[C:7]=3[C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)[CH:16]=[CH:17]2)=[N:21]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58529316HCID 58529316, compound

Product 1

HCID 58529276HCID 58529276, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]propan-1-ol (step 4, example 24, 3.40 g, 8.53 mmol) in anhydrous THF (85 mL) at 0° C. was added carbon tetrabromide (3.68 g, 11.0 mmol, 1.3 eq) and triphenylphosphine (2.46 g, 9.4 mmol, 1.1 eq), and the reaction mixture was stirred at RT for 16 h. The reaction was poured into EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated at reduced pressure. The crude product was purified by MPLC eluted with 15% acetone/DCM to give 2.45 g (62.4%) of desired product as a white solid. 1H-NMR (DMSO-d6) 8.52 (s, 1H), 7.89 (s, 1H), 7.78 (d, 1H), 7.57 (s, 1H), 7.15 to 7.35 (m, 5H), 7.13 (d, 1H), 6.62 (s, 1H), 5.74 (s, 2H), 3.61 (t, 2H), 3.03 (t, 2H), 2.22 to 2.26 (m, 2H); LC-MS [M+H]+=461/463, RT=3.16 min.

Workup

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure
  5. customThe crude product was purified by MPLC
  6. washeluted with 15% acetone/DCM

Sources & evidence

ORD record
ord-3cbb9a48825b476790d4d688a862dd26
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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