Trifluoroacetic acid → HCID 56644102, compound

HRID 2370946Notes

Reaction equation

HRID 2370946 reaction equation
Cl.Cl[C:3]1[N:8]=[C:7]([NH:9][CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[C:6]([F:20])=[CH:5][N:4]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH:32]=[N:31][N:30]=[N:29]2)=[CH:24][C:23]=1[NH2:33].[C:34](O)(C(F)(F)F)=[O:35].N1C=CC=NC=1>CC(O)C>[NH3:4].[CH3:34][OH:35].[F:20][C:6]1[C:7]([NH:9][CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)=[N:8][C:3]([NH:33][C:23]2[CH:24]=[C:25]([N:28]3[CH:32]=[N:31][N:30]=[N:29]3)[CH:26]=[CH:27][C:22]=2[F:21])=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid3×HCID 9260Pyrimidine2×HCID 163949822-Fluoro-5-(1H-tetrazol-1-yl)anilineHCID 86653878HCID 86653878, compound

Product 2

HCID 21705897Ammonia methanolYield 1%HCID 56644102HCID 56644102, compoundYield 135.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent3×

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (100 mg, 0.309 mmol, 1 equiv), 2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (90 mg, 0.495 mmol, 1.6 equiv., Chembridge, San Diego, Calif.), and TFA (100 μL, 1.24 mmol, 4 equiv) in IPA (3 mL) were heated to 100° C. in shaker overnight affording a melt. LCMS indicated pyrimidine:product ratio=29:71. IPA (1 mL) and TFA (100 μL, 1.24 mmol, 4 equiv) were added and the mixture was heated to 100° C. in shaker overnight affording a melt. LCMS indicated pyrimidine:product=4:96. IPA (1 mL) and TFA (1000 μL, 12.4 mmol, 40 equiv) were added and the mixture was heated to 100° C. in shaker for an additional 5 hours affording a melt. LCMS indicated complete conversion to product. The crude solid was quenched with 2M NH3/MeOH (1-2 mL), and diluted with DCM (3-5 mL), then loaded into a column packed with silica and filled with DCM. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 96:4 using 1% 2M NH3/MeOH increments to provide the desired product (90 mg, 68%) as a solid.

Workup

  1. customaffording a melt
  2. temperaturethe mixture was heated to 100° C. in shaker overnight
  3. customaffording a melt
  4. temperaturethe mixture was heated to 100° C. in shaker for an additional 5 hours
  5. customaffording a melt
  6. customThe crude solid was quenched with 2M NH3/MeOH (1-2 mL)
  7. additiondiluted with DCM (3-5 mL)
  8. additionfilled with DCM
  9. customThe crude product was purified by flash chromatography
  10. washeluted with DCM

Sources & evidence

ORD record
ord-cc4494555908444f92bb3607bf3607d0
Source dataset
uspto-grants-2014_04
Patent number
US08710223B2

Reaction notes

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