Sodium Carbonate → N'-{4-[4-(2-{[(3R,3aR,6R,6aR)-6-Hydroxy-hexahydrofuro[3,2-b]furan-3-yl]oxy}-6-chloro-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-5-yl)phenyl]phenyl}-N,N-dimethyl-methanesulfonimidamide

HRID 1485608Notes

Reaction equation

HRID 1485608 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:25]=[C:24]([O:26][C@H:27]3[C@H:31]4[O:32][CH2:33][C@@H:34]([OH:35])[C@H:30]4[O:29][CH2:28]3)[N:23]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=1.Br[C:45]1[CH:50]=[CH:49][C:48]([N:51]=[S:52]([CH3:57])([N:54]([CH3:56])[CH3:55])=[O:53])=[CH:47][CH:46]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C>[OH:35][C@H:34]1[C@H:30]2[O:29][CH2:28][C@@H:27]([O:26][C:24]3[N:23]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:5]4=[N:6][C:7]([C:8]5[CH:9]=[CH:10][C:11]([C:45]6[CH:46]=[CH:47][C:48]([N:51]=[S:52]([CH3:57])([N:54]([CH3:55])[CH3:56])=[O:53])=[CH:49][CH:50]=6)=[CH:12][CH:13]=5)=[C:2]([Cl:1])[CH:3]=[C:4]4[N:25]=3)[C@H:31]2[O:32][CH2:33]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 118863925N'-(4-Bromophenyl)-N,N-dimethyl-methanesulfonimidamideHCID 123678375(3R,3aR,6R,6aR)-6-(6-Chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol

Product 1

HCID 131736735N'-{4-[4-(2-{[(3R,3aR,6R,6aR)-6-Hydroxy-hexahydrofuro[3,2-b]furan-3-yl]oxy}-6-chloro-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-5-yl)phenyl]phenyl}-N,N-dimethyl-methanesulfonimidamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (3R,3aR,6R,6aR)-6-(6-chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol (1.00 g), N′-(4-bromophenyl)-N,N-dimethyl-methanesulfonimidamide (484 mg), Na2CO3 (2 M aqueous solution, 1.98 mL), and ethanol (8 mL) is purged for 5 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium(II)-CH2Cl2-complex (PdCl2(dppf)×CH2Cl2) (130 mg) is added and the mixture is stirred over night at 70° C. The reaction mixture concentrated in vacuo and the residue is purified by preparative HPLC to give the title compound. LC (method 1): tR=1.13 min; Mass spectrum (ESI+): m/z=700 [M+H]+.

Workup

  1. customis purged for 5 minutes with argon
  2. addition[1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium(II)-CH2Cl2-complex (PdCl2(dppf)×CH2Cl2) (130 mg) is added
  3. concentrationThe reaction mixture concentrated in vacuo
  4. customthe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-add0b0af03dc45f7971964beb753392f
Source dataset
uspto-grants-2016_08
Patent number
US09422312B2

Reaction notes

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