Sodium Bicarbonate → HCID 22055246, compound

HRID 1829913Notes

Reaction equation

HRID 1829913 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][N:6]2[C:11]=1[C:10](Cl)=[N:9][CH:8]=[N:7]2.C(OC([N:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1)=O)(C)(C)C.C([O-])(O)=O.[Na+].[Cl:32][C:33]1[CH:34]=[C:35]([NH2:48])[CH:36]=[CH:37][C:38]=1[O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[CH:42]=1>C(#N)C>[Cl:32][C:33]1[CH:34]=[C:35]([NH:48][C:10]2[C:11]3=[C:3]([CH2:2][O:26][CH:23]4[CH2:22][CH2:21][NH:20][CH2:25][CH2:24]4)[CH:4]=[CH:5][N:6]3[N:7]=[CH:8][N:9]=2)[CH:36]=[CH:37][C:38]=1[O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[CH:42]=1

Participants

6

Reactant 4

HCID 516892Sodium Bicarbonate2×HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 218743865-(Bromomethyl)-4-chloropyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 22055246HCID 22055246, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (100 mg, 0.408 mmole), 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.56 gm, 7.76 mmole) and NaHCO3 (131 mg, 1.56 mmol) in dry acetonitrile (5 mL) was stirred at RT for 3 days. 3-chloro-4-(3-fluoro-benzyloxy)-phenylamine 3A (92 mg, 0.367 mmole) and additional NaHCO3 (131 mg, 1.56 mmol) were added and the reaction was left stirring overnight. The solvent was removed and the residue was partitioned between DCM and water. The organic phase was separated, dried (Na2SO4), and the solvent removed. The residue was treated with a mixture of TFA:DCM (1:1) at 0° C. for 80 min and the solvents were removed. The residue was taken up in DCM, washed with a sat. aq. NaHCO3 solution and then dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate eluted with DCM containing 5% of a 2 M solution of NH3 in MeOH) afforded the titled product as an oil (85 mg, 43%). Analytical HPLC retention time=1.60 min. (YMC Xterra S7 C18, 3.0×50 mm column, 10–90% aqueous methanol over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm) and a LC/MS M++1=482.

Workup

  1. waitthe reaction was left
  2. customThe solvent was removed
  3. customthe residue was partitioned between DCM and water
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed
  7. additionThe residue was treated with a mixture of TFA:DCM (1:1) at 0° C. for 80 min
  8. customthe solvents were removed
  9. washwashed with a sat. aq. NaHCO3 solution
  10. dry with materialdried (Na2SO4)
  11. customRemoval of the solvent
  12. washeluted with DCM containing 5% of a 2 M solution of NH3 in MeOH)

Sources & evidence

ORD record
ord-798e2d8d30a1495b9438b2b8b02b38c7
Source dataset
uspto-grants-2006_06
Patent number
US07064203B2

Reaction notes

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