3-Pyridinecarboxaldehyde → 1-Cyclopentyl-3-ethyl-N-[(pyridin-3-yl)methyl]-1H-indazol-6-amine

HRID 1441916Notes

Reaction equation

HRID 1441916 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=O)[CH:2]=1.[NH2:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH2:24][CH3:25])=[N:15][N:16]2[CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:12][CH:11]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>CO.CC(=O)OCC>[CH:19]1([N:16]2[C:17]3[C:13](=[CH:12][CH:11]=[C:10]([NH:9][CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:18]=3)[C:14]([CH2:24][CH3:25])=[N:15]2)[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 103713-PyridinecarboxaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydrideHCID 45095725HCID 45095725, compound

Product 1

HCID 685409461-Cyclopentyl-3-ethyl-N-[(pyridin-3-yl)methyl]-1H-indazol-6-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3-pyridinecarboxaldehyde (106 mg, 1.0 mol) in methanol (5.0 mL) was added 6-amino-1-cyclopentyl-3-ethyl-1H-indazole (240 mg, 1.05 mmol) and p-toluenesulfonic acid monohydrate (2.0 mg). The reaction mixture was stirred for 4 h. The flask was then cooled to 0° C. and sodium borohydride (0.09 g, 2.3 mmol) was added portion-wise over 4 h. The reaction fixture was allowed to warm to room temperature over 16 h with stirring. TLC indicated the reaction was complete (1:3 hex:EA). The solvent was evaporated and diluted with water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (5 mL), dried over sodium sulfate, and concentrated to yield the desired product. 1H NMR (300 MHz) δ 8.64 (s, 1H), 8.51 (m,1H), 7.70 (m, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.25 (m, 1H), 6.50 (m,1H), 6.33 (s,1H), 4.68 (p,J=7.8 Hz, 1H), 4.55 (br,1H), 4.40 (s,1H), 2.90 (q,J=7.7 Hz, 2H), 2.1-1.8 (m,6H), 1.8-1.6 (m,2H), 1.34 (t,J=7.7 Hz, 3H).

Workup

  1. temperatureto warm to room temperature over 16 h
  2. stirringwith stirring
  3. customThe solvent was evaporated
  4. additiondiluted with water (10 mL)
  5. extractionextracted with ethyl acetate (2×20 mL)
  6. washThe combined organic layers were washed with brine (5 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-17a99b2f0d594ccd94af40578b404a68
Source dataset
uspto-grants-2010_02
Patent number
US07655802B2

Reaction notes

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