Methanol → methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate

HRID 1055440Notes

Reaction equation

HRID 1055440 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH2:12][N:13]1[C:19](=[O:20])[C@@H:18]([NH:21][C:22](=[O:34])[C@@H:23]([N:25]([CH3:33])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH3:24])[CH2:17][O:16][C:15]3[CH:35]=[CH:36][CH:37]=[CH:38][C:14]1=3)=[C:7]([O:39][CH3:40])[CH:6]=[CH:5]2.C1(P(C2C=CC=CC=2)C2[C:61]3[O:60][C:59]4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C[OH:84]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:28]([O:27][C:26]([N:25]([CH3:33])[C@@H:23]([CH3:24])[C:22]([NH:21][C@H:18]1[CH2:17][O:16][C:15]2[CH:35]=[CH:36][CH:37]=[CH:38][C:14]=2[N:13]([CH2:12][C:8]2[C:7]([O:39][CH3:40])=[CH:6][CH:5]=[C:4]3[C:9]=2[CH:10]=[CH:11][C:2]([C:59]([O:60][CH3:61])=[O:84])=[CH:3]3)[C:19]1=[O:20])=[O:34])=[O:32])([CH3:30])([CH3:31])[CH3:29]

Participants

5

Reactant 3

HCID 887MethanolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 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 118574109methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoateYield 714.3%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

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 (1.8 g, 2.94 mmol, Eq: 1.00), Pd(OAc)2 (33.0 mg, 147 μmol, Eq: 0.05) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (170 mg, 294 μmol, Eq: 0.10) in a microwave tube was evacuated and purged with N2. MeOH (1.43 g, 1.8 mL, 44.5 mmol, Eq: 15.1) and TEA were added, the vessel was purged with CO and heated at 70° C. under CO overnight. The mixture was concentrated and the residue was purified by silica gel chromatography to afford methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate (1.24 g, 2.1 mmol, 71.3%).

Workup

  1. customwas evacuated
  2. custompurged with N2
  3. customthe vessel was purged with CO
  4. concentrationThe mixture was concentrated
  5. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ad0b602a197646819541aba6aa2dd6e5
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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