Triethylamine → 1-{(R)-3-[2-(4-{1-[2-(2-Methoxy-ethoxy)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepan-1-yl)-ethyl]-3-phenyl-pyrrolidin-1-yl}-1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanone

HRID 2230713Notes

Reaction equation

HRID 2230713 reaction equation
I.I.[N:3]1([C:10]2[N:14]([CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[C:13]3[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=3[N:11]=2)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[CH:30][C:29]=1[C:39]([N:41]1[CH2:45][CH2:44][C@:43]([CH2:52][CH2:53]OS(C)(=O)=O)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:42]1)=[O:40].C(N(CC)CC)C>C(#N)C>[CH3:21][O:20][CH2:19][CH2:18][O:17][CH2:16][CH2:15][N:14]1[C:13]2[CH:22]=[CH:23][CH:24]=[CH:25][C:12]=2[N:11]=[C:10]1[N:3]1[CH2:9][CH2:8][CH2:7][N:6]([CH2:53][CH2:52][C@:43]2([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:44][CH2:45][N:41]([C:39]([C:29]3[CH:30]=[C:31]([N:34]4[CH:38]=[N:37][N:36]=[N:35]4)[CH:32]=[CH:33][C:28]=3[O:27][CH3:26])=[O:40])[CH2:42]2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18465026HCID 18465026, compoundHCID 86583904HCID 86583904, compound

Product 1

HCID 599022781-{(R)-3-[2-(4-{1-[2-(2-Methoxy-ethoxy)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepan-1-yl)-ethyl]-3-phenyl-pyrrolidin-1-yl}-1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoneYield 59.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Heat a mixture of 2-[1,4]diazepan-1-yl-1-[2-(2-methoxy-ethoxy)-ethyl]-1H-benzoimidazole dihydroiodide (0.71 g, 1.24 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.60 g, 1.27 mmol, example 47.2) and acetonitrile (10 mL), triethylamine (1.2 mL, 8.61 mmol) and acetonitrile (15 mL) at 85° C. for 18 hours. Quench the reaction and purify the crude product as described in Example 113 to afford 0.51 g of the title compound, Rf=0.40 (silica gel, dichloromethane:methanol:30% ammonium hydroxide, 90:10:0.1). The compound may be converted to the dihydrochloride salt by methods well known in the art.

Workup

  1. temperatureHeat
  2. customQuench
  3. customthe reaction
  4. custompurify the crude product

Sources & evidence

ORD record
ord-7360a2010dbd4e25aa1f3b5a8b3ad32a
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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