Sodium hydride → 2-[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol

HRID 1398604Notes

Reaction equation

HRID 1398604 reaction equation
[I:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH2:24])[N:19]=1>CN(C=O)C>[NH2:24][C:20]1[N:21]=[C:22]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=3)[C:6]([C:11]([OH:14])([CH3:12])[CH3:13])=[N:7]2)[CH:23]=[CH:18][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2233322-Amino-4-chloropyrimidineHCID 178458961HCID 178458961, compound

Product 1

HCID 681818982-[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(6-iodo-1H-indazol-3-yl)propan-2-ol (1.00 g, 3.31 mmol) in dry DMF (30 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (212 mg of a 60% dispersion in mineral oil, 5.3 mmol). After 20 minutes at this temperature, 4-chloropyrimidin-2-amine (858 mg, 6.62 mmol) was added and the solution warmed to RT for 10 minutes, then to 65° C. for 23 hr. The reaction mixture was cooled to RT, quenched carefully with water (20 mL) and extracted with EtOAc (2×20 mL extractions). The organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by silica gel flash column chromatography (4:1 to 1:1 heptane/EtOAc gradient) furnished the title compound as an off-white solid: 1H NMR (250 MHz, CDCl3) delta 1.73-1.83 (6H, m), 2.77 (1H, s), 5.16 (2H, s), 7.23-7.33 (1H, m), 7.55-7.64 (1H, m), 7.68-7.78 (1H, m), 8.30 (1H, d, J=5.79 Hz), 9.15-9.28 (1 H, m); LC-MS: m/z=+395.90 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customquenched carefully with water (20 mL)
  3. extractionextracted with EtOAc (2×20 mL extractions)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by silica gel flash column chromatography (4:1 to 1:1 heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-c32f26467be041469ff8132050801617
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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