Hydrochloric Acid → 1-{5-[5-fluoro-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,3-thiazol-2-yl}cyclobutanol

HRID 2362696Notes

Reaction equation

HRID 2362696 reaction equation
[F:1][C:2]1[C:3]([C:33]2[S:37][C:36]([C:38]3([OH:42])[CH2:41][CH2:40][CH2:39]3)=[N:35][CH:34]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.Cl>CO.[OH-].[Na+]>[F:1][C:2]1[C:3]([C:33]2[S:37][C:36]([C:38]3([OH:42])[CH2:41][CH2:40][CH2:39]3)=[N:35][CH:34]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 670034831-(5-(5-fluoro-1-tosyl-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

Product 1

HCID 546743781-{5-[5-fluoro-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,3-thiazol-2-yl}cyclobutanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

1-(5-(5-fluoro-1-tosyl-2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 90A) (103 mg, 0.169 mmol) in methanol (2.50 mL) and 2N aqueous sodium hydroxide solution (830 μL) was heated by microwave irradiation (Biotage, Initiator) to 120° C. for 30 minutes. The reaction was cooled to room temperature, and the pH was adjusted to ˜3 with 10% aqueous HCl solution. The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v ammonium acetate and B is acetonitrile) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.48 (bs, 1H), 8.80 (s, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.37 (m, 3H), 6.69 (s, 1H), 3.91 (s, 6H), 3.71 (s, 3H), 2.64-2.55 (m, 2H), 2.45-2.35 (m, 2H), 2.05-1.92 (m, 2H); MS ESI(+) m/z 456.1 [M+H]+.

Workup

  1. customThe resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC
  2. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes

Sources & evidence

ORD record
ord-42d4549c4590402bbc07c021753fa66f
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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