Imidazole → HCID 71252893, compound

HRID 1427411Notes

Reaction equation

HRID 1427411 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[C:13](Cl)[CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.Cl[Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28].C1C[O:39][CH2:38]C1>C(Cl)Cl>[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])=[C:13]([O:39][CH3:38])[CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 795Imidazole3×HCID 8028TetrahydrofuranHCID 139400Triisopropylsilyl chloride3×HCID 67460150HCID 67460150, compound

Product 1

HCID 71252893HCID 71252893, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-tert-butyl-1-(3-chloro-4-(hydroxymethyl)phenyl)-1H-pyrazol-5-amine (840 mg, 90% purity, 2.75 mmol) in dry THF (10 mL) under N2 was added imidazole (240 mg, 3.5 mmol) and chlorotriisopropylsilane (720 μL, 650 mg, 3.40 mmol) and the reaction mixture kept at RT for 18 hr. The resulting mixture was diluted with DCM (5.0 mL) and was treated with a second aliquot of chlorotriisopropylsilane (720 μL, 650 mg, 3.40 mmol) and after a further 5 hr with additional imidazole (240 mg, 3.50 mmol). After 20 hr the reaction mixture was treated for a third time with chlorotriisopropylsilane (360 μL, 330 mg, 1.70 mmol) and imidazole (120 mg, 1.8 mmol) and after 3 days was evaporated in vacuo. The residue was taken up into EtOAc (50 mL) and was washed with water (20 mL) and brine (10 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 0-100%, gradient elution) and then by SCX capture and release to afford a brown oil which comprised of a mixture of starting material and the desired product. This mixture was taken up into THF (1.0 mL) and was treated with chlorotriisopropylsilane (200 μL, 200 mg, 0.30 mmol) and imidazole (75 mg, 1.1 mmol) and was maintained at RT for 24 hr and then evaporated in vacuo. The residue was partitioned between EtOAc (10 mL) and water (10 mL) and the organic phase was separated and extracted brine (10 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 0-100%, gradient elution) to afford the title compound, Intermediate A16 as a yellow oil (510 mg, 37%); Rt 5.74 min (Method 1 basic); m/z 432 (M+H)+, (ES+).

Workup

  1. customwas evaporated in vacuo
  2. washwas washed with water (20 mL) and brine (10 mL)
  3. customdried
  4. customevaporated in vacuo
  5. customThe residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 0-100%, gradient elution)
  6. customby SCX capture and release to afford a brown oil which
  7. additioncomprised of a mixture of starting material

Sources & evidence

ORD record
ord-0998813e5941422e9e0a9f28fcb9ea77
Source dataset
uspto-grants-2015_01
Patent number
US08933228B2

Reaction notes

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