Water → 3-[4-(3-Hydroxy-8-aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1888482Notes

Reaction equation

HRID 1888482 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:31]=[N:30][C:12]3[N:13]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4[CH:19]=[N:18][C:17]([C:20]#[N:21])=[CH:16][C:15]=4[C:11]=3[CH:10]=2)O1.Br[C:34]1[CH:49]=[CH:48][C:37]([CH2:38][N:39]2[CH:44]3[CH2:45][CH2:46][CH:40]2[CH2:41][CH:42]([OH:47])[CH2:43]3)=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:47][CH:42]1[CH2:41][CH:40]2[N:39]([CH2:38][C:37]3[CH:36]=[CH:35][C:34]([C:9]4[CH:31]=[N:30][C:12]5[N:13]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])[C:14]6[CH:19]=[N:18][C:17]([C:20]#[N:21])=[CH:16][C:15]=6[C:11]=5[CH:10]=4)=[CH:49][CH:48]=3)[CH:44]([CH2:45][CH2:46]2)[CH2:43]1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 582666493-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileHCID 582668338-[(4-Bromophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-ol

Product 1

HCID 582664623-[4-(3-Hydroxy-8-aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 60%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (217 mg, 0.48 mmol), 8-(4-bromobenzyl)-8-aza-bicyclo[3.2.1]octan-3-ol (157 mg, 0.53 mmol), tetrakis(triphenylphosphine)palladium(0) (33 mg, 5 mol %) and cesium carbonate (157 mg, 0.48 mmol) in a mixture of DME (5 mL), IMS (2 mL) and water (1.3 mL) was heated under microwave irradiation at 100° C. for 30 minutes. The cooled reaction mixture was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% (2N ammonia in MeOH) in DCM) to afford the title compound as an off-white solid (155 mg, 60%). 1H NMR (CDCl3, 300 MHz): 9.21-9.17 (m, 1H), 8.95 (d, J=2.1 Hz, 1H), 8.61 (d, J=2.1 Hz, 1H), 8.43 (s, 1H), 7.67-7.53 (m, 4H), 6.04 (s, 2H), 3.70-3.58 (m, 4H), 3.35-3.15 (m, 2H), 2.20-1.60 (m, 10H), 0.95 (t, J=8.2 Hz, 2H), 0.00 (s, 9H). LCMS (Method B): RT=2.92 min, M+H+=540.

Workup

  1. customThe cooled reaction mixture
  2. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-5% (2N ammonia in MeOH) in DCM)

Sources & evidence

ORD record
ord-5dd6c16753c3423793b29c978ed7fa24
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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