Sodium Iodide → 1-[(R)-3-(2-{4-[1-(2-Cyclopropylmethoxy-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 2230716Notes

Reaction equation

HRID 2230716 reaction equation
[CH:1]1([CH2:4][O:5][CH2:6][CH2:7][N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[N:17]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:3][CH2:2]1.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:36]=[N:35][N:34]=[N:33]2)=[CH:28][C:27]=1[C:37]([N:39]1[CH2:43][CH2:42][C@:41]([CH2:50][CH2:51]OS(C)(=O)=O)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:40]1)=[O:38].C(N(CC)CC)C.[I-].[Na+]>C(#N)C>[CH:1]1([CH2:4][O:5][CH2:6][CH2:7][N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[N:17]2[CH2:23][CH2:22][CH2:21][N:20]([CH2:51][CH2:50][C@:41]3([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[CH2:42][CH2:43][N:39]([C:37]([C:27]4[CH:28]=[C:29]([N:32]5[CH:36]=[N:35][N:34]=[N:33]5)[CH:30]=[CH:31][C:26]=4[O:25][CH3:24])=[O:38])[CH2:40]3)[CH2:19][CH2:18]2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 184644951-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazoleHCID 86583904HCID 86583904, compound

Product 1

HCID 599022701-[(R)-3-(2-{4-[1-(2-Cyclopropylmethoxy-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 70.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
81 °C

Procedure

Heat at 81° C. a mixture of 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole (0.10 g, 0.33 mmol) and 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), triethylamine (0.136 mL, 3 equivalents), sodium iodide (0.097 g, 2 equivalents) and acetonitrile (8.1 mL) under argon for 30 hours. Quench the reaction as described in Example 113. Purify the crude material by column chromatography (silica gel, 4.5 cm×15 cm, using step gradient elution with 0%, 5% and 10% methanol in dichloromethane. Concentrate the appropriate fractions to afford 0.16 g of the title compound, Rf=0.33 (silica gel, 10% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt, m.p. 135-155° C. (dec.), by methods well known in the art.

Workup

  1. customQuench
  2. customthe reaction
  3. customPurify the crude material by column chromatography (silica gel, 4.5 cm×15 cm
  4. washstep gradient elution with 0%, 5% and 10% methanol in dichloromethane
  5. concentrationConcentrate the appropriate fractions

Sources & evidence

ORD record
ord-43c9975bef544bd6ac44071cf4c77db3
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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