2-((S)-1-tert-butoxycarbonyl-pyrrolidin-2-yl)-5-tributylstannanyl-imidazole-1-carboxylic acid tert-butyl ester → (S)-2-{5-[5-(4-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3,2-b]thiophen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 716539Notes

Reaction equation

HRID 716539 reaction equation
[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[S:31][C:30]4[CH:32]=[C:33](Br)[S:34][C:29]=4[CH:28]=3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(OC([N:44]1[C:48]([Sn](CCCC)(CCCC)CCCC)=[CH:47][N:46]=[C:45]1[C@@H:62]1[CH2:66][CH2:65][CH2:64][N:63]1[C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])=O)(C)(C)C>C1(C)C=CC=CC=1.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>[C:70]([O:69][C:67]([N:63]1[CH2:64][CH2:65][CH2:66][C@H:62]1[C:45]1[NH:46][C:47]([C:33]2[S:34][C:29]3[CH:28]=[C:27]([C:24]4[CH:25]=[CH:26][C:21]([C:18]5[NH:17][C:16]([C@@H:12]6[CH2:13][CH2:14][CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:36])[CH:6]([CH3:8])[CH3:7])=[N:20][CH:19]=5)=[CH:22][CH:23]=4)[S:31][C:30]=3[CH:32]=2)=[CH:48][N:44]=1)=[O:68])([CH3:73])([CH3:71])[CH3:72]

Participants

5

Reactant 2

HCID 672401812-((S)-1-tert-butoxycarbonyl-pyrrolidin-2-yl)-5-tributylstannanyl-imidazole-1-carboxylic acid tert-butyl esterHCID 68330854[(S)-1-((S)-2-{5-[4-(5-bromo-thieno[3,2-b]thiophen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

Product 1

HCID 67240543(S)-2-{5-[5-(4-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3,2-b]thiophen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of compound 62 (0.131 mmol), compound 61 (0.141 mmol), and Pd(PPh3)4 (0.017 mmol) was refluxed in dry toluene under nitrogen overnight. Solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (eluent: DCM to DCM/MeOH 5%) to give compound 63 as an orange solid in 43% yield. MS (ESI, EI+) m/z=744.6 (MH+).

Workup

  1. customSolvent was removed under reduced pressure
  2. customThe residue was purified by silica gel chromatography (eluent: DCM to DCM/MeOH 5%)

Sources & evidence

ORD record
ord-e1a5207cf55c48bea8e5ac96ad4af01b
Source dataset
uspto-grants-2015_11
Patent number
US09187496B2

Reaction notes

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