2,6-Dimethylmorpholine, cis- → HCID 58466313, compound

HRID 335836Notes

Reaction equation

HRID 335836 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:26]4[CH:31]=[N:30][CH:29]=[CH:28][N:27]=4)=[CH:16][C:17]=3[C@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[C:9]([F:32])[CH:8]=1)(=O)=O.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.[CH3:56][C@H:57]1[O:62][C@@H:61]([CH3:63])[CH2:60][NH:59][CH2:58]1.[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].O>[CH3:56][C@@H:57]1[CH2:58][N:59]([C:7]2[CH:8]=[C:9]([F:32])[C:10]3[O:11][C:12]4[C:17](=[CH:16][C:15]([C:26]5[CH:31]=[N:30][CH:29]=[CH:28][N:27]=5)=[CH:14][CH:13]=4)[C@@:18]4([CH2:24][O:23][C:22]([NH2:25])=[N:21]4)[C:19]=3[CH:20]=2)[CH2:60][C@H:61]([CH3:63])[O:62]1

Participants

7

Reactant 4

HCID 6415002,6-Dimethylmorpholine, cis-HCID 2733832Lithium HexamethyldisilazideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86658466HCID 86658466, compound

Product 1

HCID 58466313HCID 58466313, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A microwave vial was charged with (S)-2-amino-5′-fluoro-2′-(pyrazin-2-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (150 mg, 0.302 mmol), Pd2(dba)3 (13.84 mg, 0.015 mmol), biphenyl-2-yldi-tert-butylphosphine (10.82 mg, 0.036 mmol) and (2R,6S)-2,6-dimethylmorpholine (104 mg, 0.907 mmol) and capped under argon. LiHMDS (1 M in THF) (1.511 mL, 1.511 mmol) was added and the mixture was heated in the microwave at 110° C. for 1 hr. To the reaction was added 1 ml of water and the mixture was concentrated in vacuo. The product was purified via Gilson HPLC (gradient elution 20-70% MeCN/H2O, 0.1% TFA) and freebased with sodium bicarbonte to afford (S)-2′-((2R,6S)-2,6-dimethylmorpholino)-4′-fluoro-7′-(pyrazin-2-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as an off white solid. MS m/z=462.0 [M+H].

Workup

  1. customcapped under argon
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe product was purified via Gilson HPLC (gradient elution 20-70% MeCN/H2O, 0.1% TFA) and freebased with sodium bicarbonte

Sources & evidence

ORD record
ord-7180dd305dca4b659c53ca82cd86d681
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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