Cesium carbonate → 1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one

HRID 571071Notes

Reaction equation

HRID 571071 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH2:25][OH:26])[CH:5]=[CH:6][CH:7]=1.[Cl:27][C:28]1[C:29](B2OC(C)(C)C(C)(C)O2)=[C:30]2[CH:36]=[CH:35][N:34]([Si](C(C)C)(C(C)C)C(C)C)[C:31]2=[N:32][CH:33]=1.C([O-])([O-])=O.[Cs+].[Cs+]>ClCCl.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1COCC1>[Cl:27][C:28]1[C:29]([C:2]2[CH:3]=[C:4]([N:8]3[CH:13]=[C:12]([O:14][CH2:15][C:16]4[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=4)[C:11](=[O:24])[CH:10]=[C:9]3[CH2:25][OH:26])[CH:5]=[CH:6][CH:7]=2)=[C:30]2[CH:36]=[CH:35][NH:34][C:31]2=[N:32][CH:33]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 453617775-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 674179621-(3-bromophenyl)-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one

Product 1

HCID 699320591-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one

Reagents, catalysts & solvents 2

HCID 178478475HCID 178478475, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To each of three 20 mL microwave tubes was added 0.5 g (1.2 mmol) 1-(3-bromo-phenyl)-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one, 0.33 g (0.45 mmol) dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane adduct, 0.51 g (1.44 mmol) 5-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine, 3.6 mL (3.6 mmol) 1 M aq. Cs2CO3, and 10 mL THF. The vials were then capped and heated by microwave to 150° C. for 12 minutes each. After cooling, the aqueous layer was removed and the organics were concentrated in vacuo. Purification by automated flash chromatography (40 g silica gel cartridge 0-10% MeOH/EtOAc over 30 min) afforded 1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one. LCMS (M+H)+ 488.4.

Workup

  1. customThe vials were then capped
  2. temperatureAfter cooling
  3. customthe aqueous layer was removed
  4. concentrationthe organics were concentrated in vacuo
  5. customPurification by automated flash chromatography (40 g silica gel cartridge 0-10% MeOH/EtOAc over 30 min)

Sources & evidence

ORD record
ord-9bbe822dc8214a1f81607a5d90cb5ba0
Source dataset
uspto-grants-2015_05
Patent number
US09024032B2

Reaction notes

Loading…