1-Isopropylhydrazine hydrochloride → HCID 86690783, compound

HRID 1471745Notes

Reaction equation

HRID 1471745 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[N:9]=[CH:8][C:7]=1[O:14][CH2:15][C:16]1[C:17](C(=O)/C(/C)=C/N(C)C)=[N:18][CH:19]=[CH:20][CH:21]=1.Cl.[CH:31]([NH:34][NH2:35])([CH3:33])[CH3:32]>CCO>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:7]([O:14][CH2:15][C:16]2[C:17]([C:2]3[N:34]([CH:31]([CH3:33])[CH3:32])[N:35]=[CH:7][C:6]=3[CH3:11])=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:8][N:9]=[C:10]([O:12][CH3:13])[CH:11]=1

Participants

4

Reactant 2

HCID 855731-Isopropylhydrazine hydrochlorideHCID 86690784HCID 86690784, compound

Product 1

HCID 86690783HCID 86690783, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To (E)-1-(3-((4-(1,3-dioxolan-2-yl)-6-methoxypyridin-3-yloxy)methyl)pyridin-2-yl)-3-(dimethylamino)-2-methylprop-2-en-1-one (crude, 230 mg, 0.58 mmol, 1 eq.) in EtOH (5 mL) was added isopropylhydrazine hydrochloride (128 mg, 1.16 mmol, 2 eq.) at rt. The mixture was heated at 80° C. for 2 h, cooled to rt, concentrated, and diluted with a mixture of EtOAc (50 mL) and NaHCO3(sat) (10.0 mL) solution. The layers were separated and aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 4-(1,3-dioxolan-2-yl)-5-((2-(1-isopropyl-4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxypyridine (48 mg, 20% for two steps). 1H NMR (400 MHz, CDCl3) δ 8.75 (dd, J=4.7, 1.4 Hz, 1H), 8.12 (d, J=8.1 Hz, 1H), 7.62 (s, 1H), 7.49-7.44 (m, 2H), 6.91 (s, 1H), 6.11 (s, 1H), 4.85-5.01 (m, 2H), 4.30-3.98 (m, 5H), 3.88 (s, 3H), 1.94 (s, 3H), 1.50 (d, J=6.7 Hz, 3H), 1.39 (d, J=6.7 Hz, 3H). LRMS (M+H+) m/z 411.2.

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. additiondiluted with a mixture of EtOAc (50 mL) and NaHCO3(sat) (10.0 mL) solution
  4. customThe layers were separated
  5. extractionaqueous layer was extracted with EtOAc three times
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. custompurified on silica gel using
  9. additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record
ord-795631a94b4041718a4818d543467729
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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