Nitrogen → tert-butyl (S)-1-((S)-5-((6-cyclopropyl-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1055439Notes

Reaction equation

HRID 1055439 reaction equation
N#N.Br[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([CH2:14][N:15]1[C:21](=[O:22])[C@@H:20]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:26])[CH2:19][O:18][C:17]3[CH:37]=[CH:38][CH:39]=[CH:40][C:16]1=3)=[C:9]([O:41][CH3:42])[CH:8]=[CH:7]2.[CH:43]1(B(O)O)[CH2:45][CH2:44]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.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>[CH:43]1([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[C:10]([CH2:14][N:15]2[C:21](=[O:22])[C@@H:20]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH3:26])[CH2:19][O:18][C:17]4[CH:37]=[CH:38][CH:39]=[CH:40][C:16]2=4)=[C:9]([O:41][CH3:42])[CH:8]=[CH:7]3)[CH2:45][CH2:44]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 72713381tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 131736358tert-butyl (S)-1-((S)-5-((6-cyclopropyl-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 12.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

For a duration of 5 min., N2 was bubbled through a mixture of tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (200 mg, 327 μmol, Eq: 1.00), cyclopropylboronic acid (33.7 mg, 392 μmol, Eq: 1.20), Na2CO3 (408 μl, 816 μmol, Eq: 2.50) in 1,4-dioxane (2 mL) then Pd(Ph3P)4 (18.9 mg, 16.3 μmol, Eq: 0.05) was added. The mixture was heated to reflux overnight, cooled and diluted with EtOAc. The mixture was washed with water, brine, dried over Na2SO4 and concentrated to give tert-butyl (S)-1-((S)-5-((6-cyclopropyl-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (24 mg, 41.8 μmol, 12.8%) which was used without purification.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperaturecooled
  4. washThe mixture was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ed5c9458376244ad83737e872952a25e
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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