p-Toluenesulfonic acid monohydrate → HCID 71811349, compound

HRID 1754414Notes

Reaction equation

HRID 1754414 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:17][CH:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[CH2:11][CH2:10]2)[C:5]([F:18])=[CH:4][N:3]=1.[NH2:19][C:20]1[C:21]([F:36])=[CH:22][C:23]([CH:33]2[CH2:35][CH2:34]2)=[C:24]([N:26]2[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]2)[CH:25]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[F:18][C:5]1[C:6]([NH:8][CH:9]2[CH2:17][CH:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[CH2:11][CH2:10]2)=[N:7][C:2]([NH:19][C:20]2[C:21]([F:36])=[CH:22][C:23]([CH:33]3[CH2:35][CH2:34]3)=[C:24]([N:26]3[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]3)[CH:25]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 58287145HCID 58287145, compoundHCID 81629389HCID 81629389, compound

Product 1

HCID 71811349HCID 71811349, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-(2-chloro-5-fluoropyrimidin-4-yl)octahydroindolizin-7-amine (54 mg, 0.2 mmol), 1-(5-amino-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5-one (52 mg, 0.21 mmol; prepared according to US20110130415 pages 43-48, which is hereby incorporated by reference in its entirety) and para-toluenesulfonic acid monohydrate (38 mg, 0.2 mmol) in isopropyl alcohol (3 ml) were combined in a sealed vial, heated to 70° C. and stirred for 2 days. After cooling, the mixture was concentrated under vacuum to leave a crude residue. The residue was purified by preparative high-performance liquid chromatography to give a solid. The solid was partitioned between EtOAc (20 ml) and 1N NaOH (20 ml). The aqueous layer was extracted with EtOAc (2×20 ml) and the combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave the product (46 mg, 47%) as a solid after freeze-drying from MeCN/H2O.

Workup

  1. customprepared
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated under vacuum
  4. customto leave a crude residue
  5. customThe residue was purified by preparative high-performance liquid chromatography
  6. customto give a solid
  7. customThe solid was partitioned between EtOAc (20 ml) and 1N NaOH (20 ml)
  8. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
  9. dry with materialthe combined organic extracts were dried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-26cd10c919cd4a28a914b79536973db8
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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