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

HRID 2362701Notes

Reaction equation

HRID 2362701 reaction equation
[F:1][C:2]1[C:3]([C:39]2[S:43][C:42]([C:44]3([OH:48])[CH2:47][CH2:46][CH2:45]3)=[N:41][CH:40]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13](C(OC(C)(C)C)=O)[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:39]2[S:43][C:42]([C:44]3([OH:48])[CH2:47][CH2:46][CH2:45]3)=[N:41][CH:40]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[NH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67002880tert-butyl 3-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-1H-indole-1-carboxylate

Product 1

HCID 670035831-(5-(5-fluoro-2-(5-methoxy-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of tert-butyl 3-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-1H-indole-1-carboxylate (Example 93B) (140 mg, 0.203 mmol) in methanol (2.00 mL) and 2N sodium hydroxide solution (670 μL) was heated by microwave irradiation (Biotage, Initiator) to 120° C. for 30 minutes. The reaction was cooled to room temperature, and the pH 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 12.19 (bs, 1H), 11.52 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=2.0 Hz, 1H), 8.04 (d, J=2.0 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.41 (d, J=3.51 Hz, 1H), 7.01 (s, 1H), 6.89 (d, J=3.51 Hz, 1H), 6.68 (s, 1H), 3.87 (s, 3H), 2.64-2.55 (m, 2H), 2.45-2.35 (m, 2H), 2.05-1.92 (m, 2H); MS ESI(+) m/z 435.0 [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-a1e44f5dfc324ff5ae5a5b6a366bef7f
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

Loading…