Isopropanol → HCID 56644307, compound

HRID 710230Notes

Reaction equation

HRID 710230 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.[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]([CH3:37])[CH3:36])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:38])=[C:26]([F:39])[CH:25]=2)[CH2:23][CH2:22]1.[CH:40]([OH:43])(C)C>>[NH3:4].[CH3:40][OH:43].[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]([CH3:37])[CH3:36])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH:38][C:3]3[N:8]=[C:7]([NH:9][CH:10]4[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]4)[C:6]([F:20])=[CH:5][N:4]=3)=[C:26]([F:39])[CH:25]=2)[CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 58065813HCID 58065813, compoundHCID 86653878HCID 86653878, compound

Product 2

HCID 21705897Ammonia methanolYield 1%HCID 56644307HCID 56644307, compoundYield 52%

Conditions

Temperature
70 °C

Procedure

A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (300 mg, 0.928 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(5-isopropyl-1H-tetrazol-1-yl)benzenamine (291 mg, 1.11 mmol, 1.2 equiv), and PTSA monohydrate (191 mg, 0.742 mmol, 0.8 equiv) in isopropyl alcohol (10 mL) were heated to 70° C. for 7 days. After cooling to ambient temperature, the crude reaction mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 2×, dried over Na2SO4, filtered, and concentrated to dryness. 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 give compound N2-(4-cyclopropyl-2-fluoro-5-(5-isopropyl-1H-tetrazol-1-yl)phenyl)-5-fluoro-N4-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine (245 mg, 52%) as a solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe crude reaction mixture
  3. concentrationwas concentrated to dryness
  4. customThe layers were separated
  5. washThe organic layer was washed with 1N NaOH 2×
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by flash chromatography
  10. washeluted with DCM

Sources & evidence

ORD record
ord-ad47022a03804a50b7be5e58971005df
Source dataset
uspto-grants-2015_11
Patent number
US09181222B2

Reaction notes

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