Hydrazine hydrate (1:1) → HCID 178434172, compound

HRID 1913224Notes

Reaction equation

HRID 1913224 reaction equation
[C:1]([C:4]1[C:5]([CH2:26][CH:27]2[CH2:32][CH2:31][CH:30]([C:33]([O:35]CC)=[O:34])[CH2:29][CH2:28]2)=[N:6][C:7]2[N:8]([N:11]=[CH:12][C:13]=2[C:14]2[CH:15]=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:18][CH:19]=2)[C:9]=1[NH2:10])(=O)[CH3:2].O.[NH2:39]N>CN1C(=O)CCC1>[CH3:2][C:1]1[C:4]2[C:5]([CH2:26][CH:27]3[CH2:28][CH2:29][CH:30]([C:33]([OH:35])=[O:34])[CH2:31][CH2:32]3)=[N:6][C:7]3[N:8]([N:11]=[CH:12][C:13]=3[C:14]3[CH:15]=[N:16][C:17]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:18][CH:19]=3)[C:9]=2[NH:10][N:39]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 69929788HCID 69929788, compound

Product 1

HCID 178434172HCID 178434172, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a 20 mL scintillation vial was charged ethyl 4-((6-acetyl-7-amino-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)cyclohexanecarboxylate (Int-4o, 72 mg, 0.144 mmol). To this vial was added NMP (2 mL) followed by hydrazine monohydrate (1 mL). The reaction was stirred at room temperature for 18 hours. At 18 hours, the hydrazine monohydrate was removed in vacuo and the crude 4-((7-amino-6-(1-hydrazonoethyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)cyclohexanecarbohydrazide (Int-4p) was transferred into 2-5 mL microwave vessel. The vial was sealed and heated to 200° C. for 45 minutes in microwave. After 45 minutes, the NMP was removed in vacuo using chlorobenzene as a cosolvent. The residue was dried on high vacuum over night. The crude 4-((3-methyl-6-(6-phenylpyridin-3-yl)-1H-dipyrazolo[1,5-a:4′,3′-e]pyrimidin-4-yl)methyl)cyclohexanecarbohydrazide (Int-4q) was taken up in 4 N HCl in 1,4-dioxane (2 mL). To this was added H2O (1 mL). This solution was stirred at 70° C. for 2 hours. After 2 hours, the solvent was removed in vacuo. The residue was purified via reverse-phase preparatory HPLC to yield 4-((3-methyl-6-(6-phenylpyridin-3-yl)-1H-dipyrazolo[1,5-a:4′,3′-e]pyrimidin-4-yl)methyl)cyclohexanecarboxylic acid (5) (m+H=467.23, retention time=3.66 min).

Workup

  1. waitAt 18 hours
  2. customthe hydrazine monohydrate was removed in vacuo
  3. customthe crude 4-((7-amino-6-(1-hydrazonoethyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)cyclohexanecarbohydrazide (Int-4p) was transferred into 2-5 mL microwave vessel
  4. customThe vial was sealed
  5. temperatureheated to 200° C. for 45 minutes in microwave
  6. waitAfter 45 minutes
  7. customthe NMP was removed in vacuo
  8. customThe residue was dried on high vacuum over night
  9. additionTo this was added H2O (1 mL)
  10. stirringThis solution was stirred at 70° C. for 2 hours
  11. waitAfter 2 hours
  12. customthe solvent was removed in vacuo
  13. customThe residue was purified via reverse-phase preparatory HPLC

Sources & evidence

ORD record
ord-be144981d09b470384976ec951556d2c
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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