Triphenylphosphine → HCID 86693390, compound

HRID 575352Notes

Reaction equation

HRID 575352 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13]([CH2:20]O)=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:22]=1.[CH3:23][C:24]1[NH:25][C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:11]3[CH2:10][CH:9]([CH2:12]3)[N:8]3[C:13]([CH2:20][N:25]4[C:26]5[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=5[N:28]=[C:24]4[CH3:23])=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:22]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 119842-MethylbenzimidazoleHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 86693391HCID 86693391, compound

Product 1

HCID 86693390HCID 86693390, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

10-bromo-3-formyl-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate was subjected to General Procedure 0 (ketone/aldehyde reduction) to afford crude methyl 10-bromo-3-(hydroxymethyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate. To a reaction flask was placed a solution of methyl 10-bromo-3-(hydroxymethyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate (1 eq), 2-methylbenzimidazole (1.05 eq) and triphenylphosphine (1.20 equiv) in tetrahydrofuran. This was followed by the addition of di-tert-butylazodicarboxylate (1.1 eq) in Tetrahydrofuran (1.0 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 3 hours at room temperature. The resulting mixture was extracted with dichloromethane and saturated ammonium chloride. The residue was purified by flash column chromotography to afford 114 mg (43%) of methyl 10-bromo-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate as a light yellow oil. 10-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate was subjected to General Procedure L to afford 89 mg (81%) of 10-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide as a white solid. 10-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide was reacted with (3R)-3-ethynyl-3-hydroxy-1-methyl-pyrrolidin-2-one similarly to as described in General Procedure F with non-critical modifications to afford 6.8 mg (15.1%) of 10-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-pyrrolidin-3-yl]ethynyl]-3-[(2-methylbenzimidazol-1-yl)methyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide.

Workup

  1. customTo a reaction flask was placed
  2. stirringThe resulting solution was stirred for 3 hours at room temperature
  3. extractionThe resulting mixture was extracted with dichloromethane and saturated ammonium chloride
  4. customThe residue was purified by flash column chromotography

Sources & evidence

ORD record
ord-3f7d040dc4394677b0db81c3c91a0b0c
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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