HCID 59278441, compound → HCID 59278513, compound

HRID 1698201Notes

Reaction equation

HRID 1698201 reaction equation
[CH3:1][O:2][C:3](=[O:51])[C@@H:4]([NH:26][C:27](=O)[CH:28]([NH:31][C:32]([C:34]1[C:35]2[CH:42]=[N:41][N:40]([C:43]3[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=3)[C:36]=2[CH:37]=[N:38][CH:39]=1)=[O:33])[CH2:29][CH3:30])[CH2:5][S:6]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH3:1][O:2][C:3]([C@@H:4]1[CH2:5][S:6][C:27]([CH:28]([NH:31][C:32]([C:34]2[C:35]3[CH:42]=[N:41][N:40]([C:43]4[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=4)[C:36]=3[CH:37]=[N:38][CH:39]=2)=[O:33])[CH2:29][CH3:30])=[N:26]1)=[O:51]

Participants

4

Reactant 1

HCID 59278441HCID 59278441, compound

Product 1

HCID 59278513HCID 59278513, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-2-(2-{[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]amino}-butyrylamino)-3-tritylsulfanyl-propionic acid methyl ester (0.560 g, 0.798 mmol) in CH2Cl2 (24.0 mL) was added a 1 M solution of TiCl4 (2.40 mL, 2.40 mmol) in CH2Cl2. After 2 hours, the resulting mixture was quenched with saturated aqueous sodium bicarbonate (10 mL). The aqueous layer was separated and extracted with CH2Cl2 (2×10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The mixture was purified by silica gel chromatography eluting with a gradient of 0-80% ethyl acetate in heptane to afford (R)-2-(1-{[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]amino}-propyl)-4,5-dihydro-thiazole-4-carboxylic acid methyl ester.

Workup

  1. customthe resulting mixture was quenched with saturated aqueous sodium bicarbonate (10 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with CH2Cl2 (2×10 mL)
  4. washThe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe mixture was purified by silica gel chromatography
  9. washeluting with a gradient of 0-80% ethyl acetate in heptane

Sources & evidence

ORD record
ord-3ac36cf2758f4fd0af9b1974d23a1ea7
Source dataset
uspto-grants-2012_04
Patent number
US08163918B2

Reaction notes

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