Isopropanol → Ammonia methanol

HRID 710217Notes

Reaction equation

HRID 710217 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[CH:25]=[C:26]([NH2:36])[CH:27]=[C:28]([N:31]3[CH:35]=[N:34][N:33]=[N:32]3)[C:29]=2[F:30])[CH2:23][CH2:22]1.N1C=NN=N1.C[CH:43]([OH:45])C>>[NH3:4].[CH3:43][OH:45].[CH:21]1([C:24]2[CH:25]=[C:26]([NH:36][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)[CH:27]=[C:28]([N:31]3[CH:35]=[N:34][N:33]=[N:32]3)[C:29]=2[F:30])[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 58065794HCID 58065794, compoundHCID 86653878HCID 86653878, compoundHCID 178418441HCID 178418441, compound

Product 2

HCID 21705897Ammonia methanolYield 1%HCID 56644518HCID 56644518, compound

Conditions

Temperature
70 °C

Procedure

A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (246 mg, 0.760 mmol, 1 equiv), 3-cyclopropyl-4-fluoro-5-(1H-tetrazol-1-yl)benzenamine (200 mg, 0.912 mmol, 1.2 equiv), and PTSA monohydrate (116 mg, 0.608 mmol, 0.8 equiv) in IPA (8 mL) were heated to 70° C. for 3 days. LCMS indicated 2-4% of the cleaved tetrazole product. After cooling to ambient temperature, the crude mixture was quenched with 2M NH3/MeOH followed by concentrating to dryness and repeating twice. 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 which was recrystallized with IPA/hexane to give desired compound (154 mg, 43%) as a solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe crude mixture was quenched with 2M NH3/MeOH
  3. concentrationby concentrating to dryness
  4. customThe crude product was purified by flash chromatography
  5. washeluted with DCM

Sources & evidence

ORD record
ord-21cbd796027a49e7babf7f282a927d76
Source dataset
uspto-grants-2015_11
Patent number
US09181222B2

Reaction notes

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