Sodium t-butoxide → HCID 178434953, compound

HRID 707388Notes

Reaction equation

HRID 707388 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16](=[O:27])[C:17]([C:20]2[C:21](Cl)=[N:22][CH:23]=[CH:24][CH:25]=2)([OH:19])[CH3:18])[CH2:12]1.CC(C)([O-])C.[Na+]>O1CCOCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([N:15]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[C@:17]([OH:19])([CH3:18])[C:16]2=[O:27])[CH2:12]1.[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([N:15]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[C@@:17]([OH:19])([CH3:18])[C:16]2=[O:27])[CH2:12]1

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 178473525HCID 178473525, compound

Product 2

HCID 178434953HCID 178434953, compoundYield 13.7%HCID 178434954HCID 178434954, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-2-(2-chloropyridin-3-yl)-2-hydroxypropanamide (0.094 g, 0.233 mmol), chloro-(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II)-methyl-tert-butyl ether adduct (Sigma Aldrich, 0.011 g, 0.014 mmol), sodium tert-butoxide (Aldrich, 0.045 g, 0.467 mmol) in Dioxane (0.933 ml) in a microwave vial was heated to 80° C. overnight. The reaction mixture was directly loaded onto a Biotage samplet. Purification by Biotage (25 g column; 0-100% EtOAc/hexane) followed by a second purification by Gilson HPLC (Gemini Gradient 10-70 method, Gemini-NX 10 u C18 column, 100×50 mm, solvets: ACN/0.1% TFA and water/0.1% TFA) to produce mixtures (R)-1-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-3-hydroxy-3-methyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one and (S)-1-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-3-hydroxy-3-methyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.0059 g, 0.016 mmol, 7% yield). M+1: 367.0. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.55 (s, 3 H) 2.53-2.72 (m, 2 H) 3.48-3.67 (m, 2 H) 4.63-4.77 (m, 1 H) 5.18-5.37 (m, 1 H) 7.03-7.18 (m, 1 H) 7.32-7.45 (m, 1 H) 7.46-7.61 (m, 2 H) 7.71-7.79 (m, 1 H) 7.79-7.88 (m, 1 H) 8.19-8.30 (m, 1 H).

Workup

  1. customPurification by Biotage (25 g column; 0-100% EtOAc/hexane)
  2. customfollowed by a second purification by Gilson HPLC (Gemini Gradient 10-70 method, Gemini-NX 10 u C18 column, 100×50 mm, solvets: ACN/0.1% TFA and water/0.1% TFA)

Sources & evidence

ORD record
ord-b02f1a1aec8744b3a29a199394324c70
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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