Methanol → methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-2',3',5',6'-tetrahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4'-pyran]-5 (4H)-yl)methyl)-6-methoxy-2-naphthoate

HRID 1055424Notes

Reaction equation

HRID 1055424 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:24](=[O:25])[C@@H:23]([NH:26][C:27](=[O:39])[C@@H:28]([N:30]([CH3:38])[C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH3:29])[C:17]3([CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[O:16][C:15]3[CH:40]=[CH:41][CH:42]=[CH:43][C:14]1=3)=[C:7]([O:44][CH3:45])[CH:6]=[CH:5]2.C1(P(C2C=CC=CC=2)C2[C:66]3[O:65][C:64]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:89]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:33]([O:32][C:31]([N:30]([CH3:38])[C@@H:28]([CH3:29])[C:27]([NH:26][C@H:23]1[C:17]2([CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[O:16][C:15]2[CH:40]=[CH:41][CH:42]=[CH:43][C:14]=2[N:13]([CH2:12][C:8]2[C:7]([O:44][CH3:45])=[CH:6][CH:5]=[C:4]3[C:9]=2[CH:10]=[CH:11][C:2]([C:64]([O:65][CH3:66])=[O:89])=[CH:3]3)[C:24]1=[O:25])=[O:39])=[O:37])([CH3:34])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 887MethanolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 131736349tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2',3',4,5,5',6'-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4'-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 118574251methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-2',3',5',6'-tetrahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4'-pyran]-5 (4H)-yl)methyl)-6-methoxy-2-naphthoate

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (0.17 g, 249 μmol, Eq: 1.00), Pd(OAc)2 (2.24 mg, 9.96 μmol, Eq: 0.04) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (11.5 mg, 19.9 μmol, Eq: 0.08) were combined in a 5 mL microwave tube, the vessel was evacuated and purged with N2. MeOH (79.8 mg, 101 μl, 2.49 mmol, Eq: 10) and TEA (0.5 mL) were added, the vessel was purged with CO gas for approximately 30 sec and placed in an oil bath heated to 70° C. After 18 h, the mixture was cooled, diluted with EtOAc, washed with 1 N HCl, H2O, and brine. The organic mixture was dried over Na2SO4, concentrated and the residue purified by flash chromatography to afford methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-2′,3′,5′,6′-tetrahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-5 (4H)-yl)methyl)-6-methoxy-2-naphthoate (110.5 mg, 67% as a light yellow foam.) MS m/z 662.3 (MH+)

Workup

  1. customthe vessel was evacuated
  2. custompurged with N2
  3. customthe vessel was purged with CO gas for approximately 30 sec
  4. customplaced in an oil bath
  5. temperaturethe mixture was cooled
  6. additiondiluted with EtOAc
  7. washwashed with 1 N HCl, H2O, and brine
  8. dry with materialThe organic mixture was dried over Na2SO4
  9. concentrationconcentrated
  10. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-5daa1ac053a04e53bfdbbb3ae905f5b6
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

Loading…