Diisopropylethylamine → 1,1-Dioxo-thiomorpholine-4-carboxylic acid {2-[5-(3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carbonyl)-benzoimidazol-1-yl]-ethyl}-amide

HRID 555302Notes

Reaction equation

HRID 555302 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([C:13]([N:15]3[CH:20]4[CH2:21][CH2:22][CH:16]3[CH2:17][CH:18]([OH:23])[CH2:19]4)=[O:14])=[CH:12][C:7]=2[N:6]=[CH:5]1.CCN(C(C)C)C(C)C.[O:33]=[S:34]1(=[O:43])[CH2:39][CH2:38][N:37]([C:40](Cl)=[O:41])[CH2:36][CH2:35]1>C1COCC1>[OH:23][CH:18]1[CH2:19][CH:20]2[N:15]([C:13]([C:11]3[CH:10]=[CH:9][C:8]4[N:4]([CH2:3][CH2:2][NH:1][C:40]([N:37]5[CH2:38][CH2:39][S:34](=[O:43])(=[O:33])[CH2:35][CH2:36]5)=[O:41])[CH:5]=[N:6][C:7]=4[CH:12]=3)=[O:14])[CH:16]([CH2:22][CH2:21]2)[CH2:17]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 216949071,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl chlorideHCID 66987621[1-(2-aminoethyl)-1H-benzimidazol-5-yl]-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)methanone

Product 1

HCID 167226131,1-Dioxo-thiomorpholine-4-carboxylic acid {2-[5-(3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carbonyl)-benzoimidazol-1-yl]-ethyl}-amideYield 2.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [1-(2-aminoethyl)-1H-benzimidazol-5-yl]-(3-hydroxy-8-azabicyclo[3.2.1]oct-8-yl)-methanone (0.2 g, 0.636 mmol) in dry THF (5 mL) was added DIPEA (0.3 mL, 1.91 mmol) at 0° C. To this reaction mixture was added 1,1-dioxo-thiomorpholine-4-carbonyl chloride slowly and stirred for 2 h at ambient temperature. The solvents were evaporated and the residue purified by preparative HPLC to afford 1,1-dioxo-thiomorpholine-4-carboxylic acid {2-[5-(3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carbonyl)-benzoimidazol-1-yl]-ethyl}-amide (0.007 g, 2.3%). MS-ESI m/z 476 (M+1); 1H-NMR (300 MHz, CD3OD) δ 1.5 (t, 1H), 1.8 (m, 4H), 2.1 (brs, 3H), 2.8 (s, 4H), 3.6 (t, 2H), 3.8 (s, 4H), 4.2 (m, 2H), 4.5 (t, 2H), 4.7 (s, 1H), 7.5 (d, 1H), 7.7 (d, 1H), 7.85 (s, 1H), 8.3 (s, 1H). HPLC (VERYPOL.M): tr=6.24 min (97%).

Workup

  1. customThe solvents were evaporated
  2. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-c5d6b4d3f5ce47e5971f9b738f7aaae2
Source dataset
uspto-grants-2011_11
Patent number
US08053431B2

Reaction notes

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