Lithium Hexamethyldisilazide → HCID 66611204, compound

HRID 1621427Notes

Reaction equation

HRID 1621427 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][CH:12]=[C:13]2[NH2:16])=[N:8]1.F[C:18]1[C:23]([C:24]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]3[N:31]([CH:34]4[CH2:39][CH2:38][CH2:37][CH2:36][O:35]4)[N:32]=[CH:33][C:25]=23)=[CH:22][CH:21]=[CH:20][N:19]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:30][C:28]1[N:27]=[C:26]2[N:31]([CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][O:35]3)[N:32]=[CH:33][C:25]2=[C:24]([C:23]2[C:18]([NH:16][C:13]3[C:14]4[C:9]([CH:10]=[CH:11][CH:12]=3)=[N:8][N:7]([CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[CH:15]=4)=[N:19][CH:20]=[CH:21][CH:22]=2)[N:29]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 59548328HCID 59548328, compoundHCID 601548222-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 66611204HCID 66611204, compoundYield 31.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (80.2 mg, 369 μmol) and 4-(2-fluoropyridin-3-yl)-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (112.0 mg, 357 μmol) in THF (1.0 mL) was stirred in an ice bath and treated dropwise with LHMDS (1.0 M in THF, 1.1 mL, 3 equiv.). The mixture was stirred for 45 min and then quenched with water (0.1 mL). The mixture was extracted into EtOAc from saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a dark residue. The residue was purified by flash chromatography on silica (25-30% EtOAc/hexane) to give N-(3-(6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (56.9 mg, 31.2% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 11.97 (br. s, 1H); 8.43-8.53 (m, 1H); 8.30-8.42 (m, 3H); 7.96 (br. s., 1H); 7.38-7.48 (m, 1H); 7.34 (d, J=7.43 Hz, 1H); 6.94-7.03 (m, 1H); 6.16 (d, J=10.17 Hz, 1H); 5.71 (d, J=9.00 Hz, 1H); 4.14 (d, J=9.98 Hz, 2H); 3.73-3.95 (m, 2H); 3.04 (s, 3H); 2.58-2.76 (m, 1H); 2.26-2.39 (m, 1H); 1.94-2.25 (m, 4H); 1.59-1.93 (m, 6H). m/z (ESI, +ve) 511.1 (M+H)+.

Workup

  1. customquenched with water (0.1 mL)
  2. extractionThe mixture was extracted into EtOAc from saturated aqueous NaHCO3
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give a dark residue
  6. customThe residue was purified by flash chromatography on silica (25-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-236079579e6d4181825090175d86e5ff
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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