Morpholine → HCID 67383066, compound

HRID 335817Notes

Reaction equation

HRID 335817 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.FC(F)(F)S(O[C:13]1[CH:26]=[C:25]2[C:16]([O:17][C:18]3[CH:19]=[CH:20][C:21]([NH:32][C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=4)=[CH:22][C:23]=3[C@:24]32[CH2:30][O:29][C:28]([NH2:31])=[N:27]3)=[C:15]([F:41])[CH:14]=1)(=O)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>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]>[F:41][C:15]1[C:16]2[O:17][C:18]3[C:23](=[CH:22][C:21]([NH:32][C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=4)=[CH:20][CH:19]=3)[C@@:24]3([CH2:30][O:29][C:28]([NH2:31])=[N:27]3)[C:25]=2[CH:26]=[C:13]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[CH:14]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 86658463HCID 86658463, compound

Product 1

HCID 67383066HCID 67383066, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

A vial was charged with morpholine (0.062 mL, 0.706 mmol), (S)-2-amino-5′-fluoro-2′-(3-methoxyphenylamino)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (127 mg, 0.235 mmol), Pd2 dba3 (10.78 mg, 0.012 mmol), (8.43 mg, 0.028 mmol). The tube was flushed with argon and LiHMDS (1M in THF) (0.942 mL, 0.942 mmol) was added and the vial sealed and heated at 110° C. in microwave reactor for 1 hr. The mixture was quenched with 1 ml of water, diluted with EtOAc, and loaded onto 2 g SCX-2 column. The column was washed with EtOAc and MeOH. The material was flushed from the column using 2M ammonia in MeOH. The derived solution was purified by silica gel chromatography to afford (S)-4′-fluoro-N7′-(3-methoxyphenyl)-2′-morpholino-5H-spiro[oxazole-4,9′-xanthene]-2,7′-diamine MS m/z=477.0 [M+H].

Workup

  1. additionwas added
  2. customthe vial sealed
  3. customThe mixture was quenched with 1 ml of water
  4. additiondiluted with EtOAc
  5. washThe column was washed with EtOAc and MeOH
  6. customThe material was flushed from the column
  7. customThe derived solution was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b953928099554b3787ebdb460cdfc479
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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