3-(4-Bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide → 3-(4-Bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

HRID 1366787Notes

Reaction equation

HRID 1366787 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[S:20][C:15]3=[CH:16][N:17]=[CH:18][CH:19]=[C:14]3[C:13]=2[NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[F:29])=[O:11])[CH2:4][O:3]1>Cl.CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[S:20][C:15]2=[CH:16][N:17]=[CH:18][CH:19]=[C:14]2[C:13]=1[NH:21][C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=1[F:29])=[O:11]

Participants

4

Reactant 1

HCID 597039053-(4-Bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 250297803-(4-Bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amideYield 27.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent

Procedure

A solution 3-(4-bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine -2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (61 mg, 0.12 mmol) and 1 drop of concentrated HCl in methanol (2 ml) was stirred at ambient temperature for 2 hours. The solvent was evaporated in vacuo and the resultant residue partitioned between dichloromethane (20 ml), water (10 ml) and saturated NaHCO3 solution (3 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo to afford a yellow oil. The resultant yellow oil was purified by flash chromatography (Si-SPE, DCM:MeOH, gradient 99:1 to 92:8) followed by trituration with methanol/acetonitrile to afford the title compound as an off-yellow solid (15 mg, 26%): LCMS (method A): RT=6.01 min, M+H+=456/458. 1H NMR (d4-MeOH, 400 MHz) 9.16 (d, J=0.8 Hz, 1H), 8.38 (d, J=5.8 Hz, 1H), 7.37-7.46 (m, 2H), 7.17 (ddd, J=8.6 Hz, 2.3 Hz, 2.2 Hz, 1H), 6.72 (dd, J=8.7 Hz, 8.7 Hz, 1H), 4.00-4.05 (m, 1H), 3.84-3.96 (m, 2H), 3.53-3.64 (m, 2H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe resultant residue partitioned between dichloromethane (20 ml), water (10 ml) and saturated NaHCO3 solution (3 ml)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil
  6. customThe resultant yellow oil was purified by flash chromatography (Si-SPE, DCM:MeOH, gradient 99:1 to 92:8)

Sources & evidence

ORD record
ord-36386136a6e8475580e47eca63b6fc6c
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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