2-Methyl-3-butyn-2-ol → 10-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575258Notes

Reaction equation

HRID 575258 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.BrC1C=CC2OCCN3C(CO)=C(I)N=C3C=2C=1.CC1NC=CN=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:61]1[CH:62]=[CH:63][C:64]2[O:70][CH2:69][CH2:68][N:67]3[C:71]([CH2:77][N:78]4[CH:82]=[CH:81][N:80]=[C:79]4[CH3:83])=[C:72]([C:74]([NH2:76])=[O:75])[N:73]=[C:66]3[C:65]=2[CH:84]=1.[CH3:85][C:86]([OH:90])([C:88]#[CH:89])[CH3:87]>O1CCCC1>[OH:90][C:86]([CH3:87])([CH3:85])[C:88]#[C:89][C:61]1[CH:62]=[CH:63][C:64]2[O:70][CH2:69][CH2:68][N:67]3[C:71]([CH2:77][N:78]4[CH:82]=[CH:81][N:80]=[C:79]4[CH3:83])=[C:72]([C:74]([NH2:76])=[O:75])[N:73]=[C:66]3[C:65]=2[CH:84]=1

Participants

8

Reactant 6

HCID 82582-Methyl-3-butyn-2-olHCID 11776TriphenylphosphineHCID 127492-MethylimidazoleHCID 97268Di-tert-butyl azodicarboxylateHCID 86693271(10-Bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-3-yl)methanolHCID 8669327210-bromo-3((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide2×

Product 1

HCID 8669327010-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Di-tert-butyl azodicarboxylate (470 mg, 1.79 mmol, 1.50 equiv) in tetrahydrofuran (2 mL) was added dropwise to a stirred solution of (10-bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-3-yl)methanol (500 mg, 1.19 mmol, 1.00 equiv)), 2-methyl-1H-imidazole (200 mg, 2.44 mmol, 2.00 equiv), and triphenylphosphine (400 mg, 1.74 mmol, 1.50 equiv) in tetrahydrofuran (3 mL) at 0° C. under nitrogen. The resulting solution was stirred for 3 h at room temperature and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 260 mg (45%) of 10-bromo-2-iodo-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineas as a colorless solid. This intermediate was converted to 10-bromo-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide similar to as described in Example 10 (carbonylative amidation). Similar to as described in General Procedure G, 10-bromo-3((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with 2-methylbut-3-yn-2-ol to give the titled compound as a colorless solid (2 mg, 2%).

Workup

  1. concentrationconcentrated under vacuum
  2. customThis resulted in 260 mg (45%) of 10-bromo-2-iodo-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineas as a colorless solid

Sources & evidence

ORD record
ord-97dc3b1e2d2a4fdd9d27a20d0ea47f67
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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