Lithium diisopropylamide → 4-[1-(2-Aminopyrimidin-4-yl)-3-methylindazol-6-yl]-2-[1-(triphenylmethyl)imidazol-4-yl]but-3-yn-2-ol

HRID 1398560Notes

Reaction equation

HRID 1398560 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH3:19])=[N:8][N:9]2[C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH2:18])[N:13]=2)=[CH:5][CH:4]=1)#[CH:2].[Li+].CC([N-]C(C)C)C.[C:28]1([C:34]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[N:35]2[CH:39]=[C:38]([C:40](=[O:42])[CH3:41])[N:37]=[CH:36]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[NH2:18][C:14]1[N:13]=[C:12]([N:9]2[C:10]3[C:6](=[CH:5][CH:4]=[C:3]([C:1]#[C:2][C:40]([C:38]4[N:37]=[CH:36][N:35]([C:34]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)[CH:39]=4)([OH:42])[CH3:41])[CH:11]=3)[C:7]([CH3:19])=[N:8]2)[CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 104280901-(1-trityl-1H-imidazol-4-yl)ethanoneHCID 866695904-(6-Ethynyl-3-methylindazol-1-yl)pyrimidin-2-amine

Product 1

HCID 681818514-[1-(2-Aminopyrimidin-4-yl)-3-methylindazol-6-yl]-2-[1-(triphenylmethyl)imidazol-4-yl]but-3-yn-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 4-(6-ethynyl-3-methylindazol-1-yl)pyrimidin-2-amine (180 mg at 90% purity, 0.65 mmol) in THF (2.5 mL) at −78° C. under nitrogen was added 2M LDA in THF (0.81 mL, 1.63 mmol). After 5 minutes 1-[1-(triphenylmethyl)imidazol-4-yl]ethanone (458.08 mg, 1.3 mmol) in THF (1.5 mL) was added. After 20 minutes, the mixture was allowed to warm up to RT and stirred for a further 1 hr. The reaction mixture was quenched by addition of saturated aqueous NH4Cl (1 mL). The volatiles were removed in vacuo and the mixture was diluted with DCM (10 ml) and washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 2-12% methanol gradient in DCM) to give the title intermediate as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 1.96 (3H, s), 2.58 (3H, s), 4.41 (1H, s), 5.36 (2H, s), 6.96 (1H, d, J=1.0), 7.19-7.09 (6H, m), 7.24 (1H, d, J=5.7 Hz), 7.35-7.30 (10H, m), 7.44 (1H, d, J=1.0 Hz), 7.53 (1H, d, J=8.2), 8.24 (1H, d, J=5.7), 8.83 (1H, s); LC-MS: m/z=+360.35 (M-C(C6H5)3)+.

Workup

  1. customThe reaction mixture was quenched by addition of saturated aqueous NH4Cl (1 mL)
  2. customThe volatiles were removed in vacuo
  3. additionthe mixture was diluted with DCM (10 ml)
  4. washwashed with water (2 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (Biotage, 2-12% methanol gradient in DCM)

Sources & evidence

ORD record
ord-4e9ec27d2394444eb563be42a03ff4ae
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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