4,7-Dichloropyrido[3,2-d]pyrimidine → (4S,6S)-4-(5-((7-chloropyrido[3,2-d]pyrimidin-4-yl)amino)-2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930425Notes

Reaction equation

HRID 930425 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH3:22])[C:5]([F:21])=[C:6]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.Cl[C:24]1[C:25]2[N:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:26]=2[N:27]=[CH:28][N:29]=1>CC(O)C.C(Cl)Cl>[Cl:34][C:31]1[CH:32]=[N:33][C:25]2[C:24]([NH:1][C:2]3[CH:3]=[C:4]([CH3:22])[C:5]([F:21])=[C:6]([C@:8]4([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:15])[F:16])[O:11][C:10]([NH2:18])=[N:9]4)[CH:7]=3)=[N:29][CH:28]=[N:27][C:26]=2[CH:30]=1

Participants

5

Reactant 2

HCID 714284454,7-Dichloropyrido[3,2-d]pyrimidineHCID 86732263HCID 86732263, compound

Product 1

HCID 86732265(4S,6S)-4-(5-((7-chloropyrido[3,2-d]pyrimidin-4-yl)amino)-2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 50%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (4S,6S)-4-(5-amino-2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.044 g, 0.136 mmol) and 4,7-dichloropyrido[3,2-d]pyrimidine (0.030 g, 0.150 mmol) in iPrOH (2 mL) was added a catalytic amount of concentrated H2 SO4 and the resulting mixture was heated in microwave at 100° C. for 45 min. The mixture was diluted with DCM, washed with 1 N NaOH and extracted with DCM. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-4% MeOH/DCM to afford a light brown solid as (4S,6S)-4-(5-((7-chloropyrido[3,2-d]pyrimidin-4-yl)amino)-2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.033 g, 0.068 mmol, 49.8% yield). MS m/z=486.9 [M+H]+. Calculated for C20H16ClF5N6O: 486.10.

Workup

  1. additionwas added a catalytic amount of concentrated H2 SO4
  2. washwashed with 1 N NaOH
  3. extractionextracted with DCM
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on silica gel using 0-4% MeOH/DCM

Sources & evidence

ORD record
ord-d69ab1c6c92b47e6885baa21effb13e9
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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