p-Toluenesulfonic acid monohydrate → HCID 178510199, compound

HRID 2175392Notes

Reaction equation

HRID 2175392 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:10]2[CH2:12][CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].Cl[C:14]1[N:19]=[C:18]([OH:20])[C:17]([Cl:21])=[CH:16][N:15]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[Cl:21][C:17]1[C:18]([OH:20])=[N:19][C:14]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH:10]3[CH2:11][CH2:12]3)=[C:6]([CH:9]=2)[C:7]#[N:8])=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 867213231552271-08-5HCID 178517823HCID 178517823, compound

Product 1

HCID 178510199HCID 178510199, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
110 °C

Procedure

5-amino-2-cyclopropylbenzonitrile (25.4 mmol; from the previous reaction) was transferred to a large reaction tube with magnetic stir bar in 250 mL isopropyl alcohol. 2,5-dichloropyrimidin-4-ol (4.20 g, 25.5 mmol) and p-toluenesulfonic acid monohydrate (14.50 g, 76.2 mmol) were weighed out and added. This was heated overnight at 110° C. After that time, it was allowed to cool to room temperature and an orange precipitate was filtered off. The filtrate was concentrated to half volume, and a second precipitate crashed out which was filtered off. Again, the filtrate was concentrated to half volume and a third precipitate crashed out which was filtered off. Finally, further concentration crashed out a fourth precipitate which was collected and washed with hexane. This was dried on high vacuum to give 5.63 g of 5-(5-chloro-4-hydroxypyrimidin-2-ylamino)-2-cyclopropylbenzonitrile as a tosylate salt, containing 1.2 equivalents of p-toluenesulfonic acid (45% yield).

Workup

  1. customfrom the previous reaction)
  2. additionadded
  3. temperatureto cool to room temperature
  4. filtrationan orange precipitate was filtered off
  5. concentrationThe filtrate was concentrated to half volume
  6. filtrationwas filtered off
  7. concentrationAgain, the filtrate was concentrated to half volume
  8. filtrationwas filtered off
  9. concentrationFinally, further concentration
  10. customwas collected
  11. washwashed with hexane
  12. customThis was dried on high vacuum

Sources & evidence

ORD record
ord-554a5a91ecc846a58c54772e191d52f8
Source dataset
uspto-grants-2015_06
Patent number
US09062068B2

Reaction notes

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