1,1'-Thiocarbonyldiimidazole → Imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl)ester

HRID 1505944Notes

Reaction equation

HRID 1505944 reaction equation
[OH:1][CH:2]1[CH2:8][CH:7]2[N:9]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:39]=[N:38][C:20]5[N:21]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:22]6[CH:27]=[N:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=6[C:19]=5[CH:18]=4)=[CH:13][CH:12]=3)[CH:4]([CH2:5][CH2:6]2)[CH2:3]1.[CH:40]1[N:44]=[CH:43][N:42]([C:45](N2C=NC=C2)=[S:46])[CH:41]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:28]([C:25]1[N:26]=[CH:27][C:22]2[N:21]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:35])([CH3:36])[CH3:37])[C:20]3[N:38]=[CH:39][C:17]([C:14]4[CH:15]=[CH:16][C:11]([CH2:10][N:9]5[CH:7]6[CH2:6][CH2:5][CH:4]5[CH2:3][CH:2]([O:1][C:45]([N:42]5[CH:41]=[CH:40][N:44]=[CH:43]5)=[S:46])[CH2:8]6)=[CH:12][CH:13]=4)=[CH:18][C:19]=3[C:23]=2[CH:24]=1)#[N:29]

Participants

5

Reactant 2

HCID 802641,1'-ThiocarbonyldiimidazoleHCID 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-carbonitrile

Product 1

HCID 58266558Imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl)esterYield 97%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[4-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (155 mg, 0.29 mmol), DMAP (5 mg, catalytic) and N,N′-thiocarbonyldiimidazole (455 mg, 8.76 mmol) in DCM (10 mL) was heated under reflux for 12 h. The cooled reaction mixture was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM) to afford the title compound as a white solid (182 mg, 97%). 1H NMR (CDCl3, 300 MHz): 9.28-9.25 (m, 1H), 9.04 (dd, J=7.0, 2.2 Hz, 1H), 8.69-8.66 (m, 1H), 8.51 (d, J=1.0 Hz, 1H), 8.47-8.39 (m, 1H), 7.81-7.61 (m, 5H), 7.15-7.10 (m, 1H), 6.12 (s, 2H), 4.35 (s, 2H), 3.76-3.61 (m, 4H), 2.32-2.17 (m, 4H), 2.13-1.93 (m, 5H), 1.08-0.96 (m, 2H), 0.00 (s, 9H). LCMS (Method B): RT=3.13 min, M+H+=650.

Workup

  1. temperatureunder reflux for 12 h
  2. customThe cooled reaction mixture
  3. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-621a433903484637aad452e3fca18ad7
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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