Dichloromethane → HCID 70355131, compound

HRID 538359Notes

Reaction equation

HRID 538359 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:20])[CH2:13][O:12][C@@:11]([CH3:18])([C:14]([F:17])([F:16])[F:15])[C:10]([NH2:19])=[N:9]2)[C:5]([F:21])=[CH:4][CH:3]=1.NC1N=C([C@@:29]2(C)[CH2:34][O:33][C@@:32]([CH3:39])([C:35](F)(F)F)[C:31](N)=[N:30]2)C(F)=CC=1.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.CC[N:60](C(C)C)C(C)C.Cl[CH2:68][Cl:69]>>[NH2:19][C:10]1[C@:11]([CH3:18])([C:14]([F:15])([F:17])[F:16])[O:12][CH2:13][C@:8]([C:6]2[N:7]=[C:2]([NH:1][C:34]([C:29]3[C:68]([Cl:69])=[CH:39][C:32]([C:35]#[N:60])=[CH:31][N:30]=3)=[O:33])[CH:3]=[CH:4][C:5]=2[F:21])([CH3:20])[N:9]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 68108097HCID 68108097, compoundHCID 68108449HCID 68108449, compound

Product 1

HCID 70355131HCID 70355131, compound

Procedure

A solution of (2R,5R)-5-(6-amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl amine and (2R,5S)-5-(6-Amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl amine (10.99 g, 35.9 mmol, ca. 3:1 mixture), Boc2O (7.05 g, 32.3 mmol) and Hünig's base (7.52 ml, 43.1 mmol) in dichloromethane (120 ml) was stirred at 0° C. for 4 hours and then at rt over night. The reaction mixture was evaporated and the residue was diluted with ethyl acetate. Crushed ice was added and the mixture was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The crude product (14.23 g) was triturated with toluene/cyclo-hexane/ethyl acetate 4:4:2, cooled and filtered. 5.14 g colorless solid. The filtrate was evaporated and the resulting mixture was filtered over silica (TBME) to give the 2 isomers as an 8:2 mixture (6.31 g). The colorless solid (5.14 g) was dissolved in dichloromethane and chromatographed over silicagel (toluene/cyclohexane/ethyl acetate 4:4:2) to afford the two isomers.

Workup

  1. waitat rt over night
  2. customThe reaction mixture was evaporated
  3. additionthe residue was diluted with ethyl acetate
  4. additionCrushed ice was added
  5. washthe mixture was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product (14.23 g) was triturated with toluene/cyclo-hexane/ethyl acetate 4:4:2
  10. temperaturecooled
  11. filtrationfiltered
  12. customThe filtrate was evaporated
  13. filtrationthe resulting mixture was filtered over silica (TBME)

Sources & evidence

ORD record
ord-615b6b9742f14eac903212a4f00658b6
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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