Methanol → HCID 118574287, compound

HRID 1055445Notes

Reaction equation

HRID 1055445 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])[C@H:17]([CH3:35])[O:16][C:15]3[CH:36]=[C:37]([CH3:40])[CH:38]=[CH:39][C:14]1=3)=[C:7]([O:41][CH3:42])[CH:6]=[CH:5]2.CC1(C)C2[C:65](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:64][C:46]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[OH:86]>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[C@H:17]([CH3:35])[O:16][C:15]2[CH:36]=[C:37]([CH3:40])[CH:38]=[CH:39][C:14]=2[N:13]([CH2:12][C:8]2[C:7]([O:41][CH3:42])=[CH:6][CH:5]=[C:4]3[C:9]=2[CH:10]=[CH:11][C:2]([C:46]([O:64][CH3:65])=[O:86])=[CH:3]3)[C:19]1=[O:20])=[O:34])=[O:32])([CH3:29])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 887MethanolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 131736360HCID 131736360, compound

Product 1

HCID 118574287HCID 118574287, compoundYield 316.8%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of tert-butyl (S)-1-((2S,3S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2,8-dimethyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (70 mg, 109 μmol, Eq: 1.00), Pd(OAc)2 (2.45 mg, 10.9 μmol, Eq: 0.1), Xantphos (12.6 mg, 21.9 μmol, Eq: 0.2), MeOH (35.0 mg, 44.2 μl, 1.09 mmol, Eq: 10), and TEA in a microwave tube was purged with CO and heated at 70° C. under CO overnight. The mixture was diluted with EtOAc, water, brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography to afford methyl 5-(((2S,3S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2,8-dimethyl-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate (43 mg, 63%)

Workup

  1. customwas purged with CO
  2. additionThe mixture was diluted with EtOAc, water, brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a8e2950be5014c75a9d36859c1d642bc
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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