Methanol → HCID 178464929, compound

HRID 246001Notes

Reaction equation

HRID 246001 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][CH:24]([C@H:26]5[CH2:29][C@H:28]([O:30]C(=O)C6C=CC([N+]([O-])=O)=CC=6)[CH2:27]5)[CH3:25])=[O:22])=[CH:19][N:18]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[OH-].[Na+].CO>C1COCC1.O>[OH:30][C@H:28]1[CH2:27][C@H:26]([CH:24]([NH:23][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:47])([CH3:49])[CH3:48])[CH:19]=2)=[O:22])[CH3:25])[CH2:29]1

Participants

6

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 178464930HCID 178464930, compound

Product 1

HCID 178464929HCID 178464929, compoundYield 72.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-nitrobenzoic acid trans-3-(1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-cyclobutyl ester (250 mg, 0.36 mmol) in THF (12 mL) was added 10% aqueous sodium hydroxide (0.44 mL, 1.09 mmol), water (1 mL), and MeOH (2 mL). The reaction mixture was stirred at room temperature for 30 min then diluted with water and extracted with CH2Cl2 (3×). The combined organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 30% to 80% EtOAc/hexanes to afford 140 mg (72%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(trans-3-hydroxy-cyclobutyl)-ethyl]-amide as an off-white solid.

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. dry with materialThe combined organics were dried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography with 30% to 80% EtOAc/hexanes

Sources & evidence

ORD record
ord-0d95b29a86cd4d73a14879413bc6035b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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