Binap, (A+-)- → HCID 67207670, compound

HRID 2041713Notes

Reaction equation

HRID 2041713 reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:34])[N:10]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25]([C:29](=[O:31])[CH3:30])[C@@H:24]([CH3:32])[CH2:23][C@H:22]4[NH2:33])=[CH:15][CH:14]=2)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Cl[C:88]1[CH:93]=[CH:92][C:91]([F:94])=[CH:90][N:89]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]1([CH2:7][O:8][C:9](=[O:34])[N:10]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25]([C:29](=[O:31])[CH3:30])[C@@H:24]([CH3:32])[CH2:23][C@H:22]4[NH:33][C:88]3[CH:93]=[CH:92][C:91]([F:94])=[CH:90][N:89]=3)=[CH:17][CH:18]=2)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 27828012-Chloro-5-fluoropyridineHCID 23676156Sodium t-butoxideHCID 67206295HCID 67206295, compound

Product 1

HCID 67207670HCID 67207670, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A flask was charged with phenylmethyl({4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate (for a preparation see intermediate 80) (100 mg, 0.219 mmol), sodium tert-butoxide (31.5 mg, 0.328 mmol), racemic BINAP (6.80 mg, 10.93 μmol), tris(dibenzylideneacetone)dipalladium(0) (10.01 mg, 10.93 μmol) and 2-chloro-5-fluoropyridine (0.033 mL, 0.328 mmol), then filled with toluene (2 mL) and the resulting mixture was stirred at 110° C. for 22 h then cooled to room temperature and partitioned between water (20 mL) and EtOAc (60 mL). The layers were separated and the aqueous phase was extracted with EtOAc (30 mL). The combined organic phases were washed with brine (30 mL), dried over MgSO4 and concentrated in vacuovacuo. Purification of this residue on SP4 using a 25 G silica cartridge (gradient:10 to 50% AcOEt in Hexanes) following by another purification using a 12 G silica cartridge (gradient:10 to 50% AcOEt in Hexanes) gave phenylmethyl[(4-{(2S,4R)-1-acetyl-4-[(5-fluoro-2-pyridinyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}phenyl)methyl]methylcarbamate (60 mg, 35%)

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between water (20 mL) and EtOAc (60 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (30 mL)
  5. washThe combined organic phases were washed with brine (30 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuovacuo
  8. customPurification of this residue on SP4
  9. customfollowing by another purification

Sources & evidence

ORD record
ord-184b48d0792a4a6eb2c5e8be9520c2ce
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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