Hydrochloric Acid → 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid

HRID 246301Notes

Reaction equation

HRID 246301 reaction equation
C[O:2][C:3](=[O:44])[CH2:4][CH2:5][CH2:6][N:7]1[C:15]2[C:10](=[CH:11][C:12]([O:16][CH:17]([F:19])[F:18])=[CH:13][CH:14]=2)[C:9]([C:20]2[N:21]=[C:22]3[C:28]([C:29](=[O:35])[NH:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][N:26]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:23]3=[N:24][CH:25]=2)=[N:8]1.CO.[OH-].[Li+].Cl>C1COCC1.O>[C:31]([NH:30][C:29]([C:28]1[C:22]2[C:23](=[N:24][CH:25]=[C:20]([C:9]3[C:10]4[C:15](=[CH:14][CH:13]=[C:12]([O:16][CH:17]([F:18])[F:19])[CH:11]=4)[N:7]([CH2:6][CH2:5][CH2:4][C:3]([OH:44])=[O:2])[N:8]=3)[N:21]=2)[N:26]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[CH:27]=1)=[O:35])([CH3:32])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 712796884-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid methyl ester

Product 1

HCID 712794494-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acidYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

In a round-bottomed flask, 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid methyl ester (98 mg, 0.155 mmol) was suspended in THF (1.1 ml), methanol (1.1 ml) and water (1.1 ml). Then, aqueous 1.0 M lithium hydroxide (0.80 ml, 0.80 mmol) was added. The light yellow suspension was stirred at 75° C. for 8 h then cooled to room temperature and stirred overnight. The reaction was diluted with water and acidified with 1 M HCl until pH=˜2 then extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was triturated with diethyl ether to afford 81 mg (85%) of 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid as a brown powder.

Workup

  1. temperaturethen cooled to room temperature
  2. stirringstirred overnight
  3. extractionthen extracted with dichloromethane (3×)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-3fdd628e341b4957ac9c8efe2cd499ca
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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