Diisobutylaluminum hydride → {2-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropyl}-methanol

HRID 1972878Notes

Reaction equation

HRID 1972878 reaction equation
C([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12]([C:20]2[CH:21]=[CH:22][C:23]3[C:27]([CH:28]=2)=[N:26][N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:24]=3)[CH:11]=1)=O)C.CC(C[AlH]CC(C)C)C>C1COCC1>[NH2:19][C:14]1[C:13]2=[C:12]([C:20]3[CH:21]=[CH:22][C:23]4[C:27]([CH:28]=3)=[N:26][N:25]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:24]=4)[CH:11]=[C:10]([CH2:9][CH:7]3[CH2:8][CH:6]3[CH2:4][OH:3])[N:18]2[N:17]=[CH:16][N:15]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydride2×HCID 585293712-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 58529545{2-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropyl}-methanolYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[4-amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl ester (3.55 g, 7.6 mmol) in THF (106 mL) at 0° C. was added DIBAL (4.3 g, 30 mmol). The reaction mixture was stirred at rt for 1.5 hour. TLC analysis showed starting material, and 20 mL of DIBAL was added. The reaction mixture was stirred at rt for another 3 hours until no starting material was detected by TLC analysis. The reaction was quenched by saturated, aqueous NH4Cl. The organic layer was separated, dried and concentrated in vacuo. The residue was purified by Biotage® (gradient 50%—100% EtOAc/hexane to 5% MeOH/EtOAc) to give the title product as an off-white solid, 2.5 g (yield 77%). 1H NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1 H), 8.05 (d, 2 H), 8.0 (s, 1 H), 7.90 (d, 1 H), 7.70 (s, 1 H), 7.60-7.40 (m, 7 H), 7.25 (d, 1 H), 7.20 (s, 1 H), 5.70 (s, 2 H), 4.6 (m, 2 H), 3.4 (m, 2 H), 2.90 (m, 2 H), 1.2-1.0 (m, 2 H); ES-MS m/z 425.33 [M+H]+, HPLC RT (min) 2.93.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at rt for another 3 hours until no starting material
  3. customThe reaction was quenched by saturated, aqueous NH4Cl
  4. customThe organic layer was separated
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Biotage® (gradient 50%—100% EtOAc/hexane to 5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-05cb7600bbf941639760c98490ace6ce
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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