HCID 21874222, compound → HCID 178521557, compound

HRID 723455Notes

Reaction equation

HRID 723455 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]3=[C:16]([CH:19]([CH:21]4[CH2:26][CH2:25][CH:24]([O:27]C(C)([Si](C)(C)C)C)[CH2:23][CH2:22]4)O)[CH:17]=[CH:18][N:14]3[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]3=[C:16]([CH2:19][C@H:21]4[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]4)[CH:17]=[CH:18][N:14]3[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 1

HCID 21874222HCID 21874222, compound

Product 1

HCID 178521557HCID 178521557, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of [4-(3-chloro-4-fluoro-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]-[4-(1-methyl-1-trimethylsilanyl-ethoxy)-cyclohexyl]-methanol (448 mg, 0.887 mmole) triethylsilane (1.03 g, 8.87 mmole) in TFA (8 mL) under N2 in a pressure flask was heated at 75° C. overnight. The solvents were removed and the residue was dissolved in CH3OH (10 ml) and solid Na2CO3 (2.0 g) was added. After stirring vigorously for 1 h, the solvent was removed and the residue was partitioned between DCM (200 ml) and H2O (50 ml). The organic phase was separated, dried over Na2SO4, and the solvent was removed. Purification via radial chromatography (2 mm silica gel plate, gradient elution with 0 to 4% NH3 in MeOH (2N) in DCM) afforded the title compound (209 mg, 63%) as a solid: MS: 375 (M+H)+; HPLC Ret Time: 1.49 min (Xterra 3.0×50 mm S7 column, 2 min gradient, 5 mL/min).

Workup

  1. customThe solvents were removed
  2. dissolutionthe residue was dissolved in CH3OH (10 ml)
  3. additionsolid Na2CO3 (2.0 g) was added
  4. customthe solvent was removed
  5. customthe residue was partitioned between DCM (200 ml) and H2O (50 ml)
  6. customThe organic phase was separated
  7. dry with materialdried over Na2SO4
  8. customthe solvent was removed
  9. customPurification
  10. washvia radial chromatography (2 mm silica gel plate, gradient elution with 0 to 4% NH3 in MeOH (2N) in DCM)

Sources & evidence

ORD record
ord-d7b6f007280c4658bd7d49059ead5b2f
Source dataset
uspto-grants-2006_11
Patent number
US07141571B2

Reaction notes

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