Sodium Hydroxide → 1-Cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

HRID 2264975Notes

Reaction equation

HRID 2264975 reaction equation
C[O:2][C:3]([C:5]1[N:13]([CH:14]2[CH2:16][CH2:15]2)[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=1[F:25])=[O:4].[OH-].[Na+]>C1COCC1.CO.O>[CH:14]1([N:13]2[C:12]3[CH:11]=[CH:10][N:9]=[CH:8][C:7]=3[C:6]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=3[F:25])=[C:5]2[C:3]([OH:4])=[O:2])[CH2:15][CH2:16]1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 595965401-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595964661-Cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acidYield 168.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (150.0 mg, 0.33 mmol) in anhydrous THF (3.5 mL) and anhydrous methanol (1.0 mL) under N2 was added freshly prepared 1N aqueous sodium hydroxide (0.66 ml, 2.0 eq). The reaction mixture was stirred at 65° C. for 1 h. The resultant reaction mixture was evaporated in vacuo and azeotroped with toluene (3×5 ml) to give a yellow solid. The yellow solid was redissolved in water (5 mL), and concentrated. Acetic acid (2 drops) was added. A yellow solid precipitated out, and the solid was filtered, rinsed well with water, and dried on high-vacuum pump to give 243.6 mg (77.4%) of the product. 1H-NMR (500 MHz, DMSO-d6) δ ppm 8.54 (s, 1H), 8.32 (d, J=6.0 Hz, 1H), 7.95 (br s, 1H), 7.65-7.52 (m, 2H), 7.33 (d, J=8.4 Hz, 1H), 6.67 (t, J=9.6 Hz, 1H), 3.53-3.28 (m, 1H), 1.20-1.07 (m, 2H), 0.85 (m, 2H); LC-MS (method C): [M+H]+=438.0, RT=0.67 min.

Workup

  1. customThe resultant reaction mixture
  2. customwas evaporated in vacuo
  3. customazeotroped with toluene (3×5 ml)
  4. customto give a yellow solid
  5. concentrationconcentrated
  6. additionAcetic acid (2 drops) was added
  7. customA yellow solid precipitated out
  8. filtrationthe solid was filtered
  9. washrinsed well with water
  10. customdried on high-vacuum pump

Sources & evidence

ORD record
ord-7d8242509bbf43f485851cebc7b46082
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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