Pyridine → 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-amine

HRID 218171Notes

Reaction equation

HRID 218171 reaction equation
[CH:1]1([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:18]([CH3:23])([CH3:22])[C:19](O)=O)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:30]1C=CC=CC=1.N1C(F)=NC(F)=NC=1F.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C(Cl)Cl>[CH:1]1([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:18]([CH3:23])([CH3:22])[CH2:19][NH2:30])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 12664Cyanuric fluorideHCID 21226445Aluminium lithium hydrideHCID 687039613-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid

Product 1

HCID 687067223-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

(c)(d)(e)(f) 3-(1-Cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (393 mg, 1 mmol) was dissolved in 20 mL DCM and treated with 130 mL pyridine and 127 uL of cyanuric fluoride and stirred overnight. The reaction was extracted from 1 M HCl with EtOAc×3. The combined organic layers were dried over MgSO4, filtered, concentrated, and then taken up in THF (20 mL), cooled to −78° C. and ammonia gas was bubbled in for 1 min. The reaction was allowed to warm to rt. Quantitative conversion to 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanamide. (M+H)+=390. This compound was dissolved in 15 mL THF and treated with LiAlH4 (4 mL, 4 mmol, 1 M in THF) and stirred for 3 h. The reaction was quenched with EtOAc and then 5 mL 1 M NaOH. After stirring 30 min, the reaction was extracted from brine 4× EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-amine. (M+H)+=376. This material was dissolved in 3 mL DCM and treated with 0.2 mL trifluoroacetic anhydride. After 3 h, the reaction was rotovapped down and purified by HPLC to give N-(3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)-2,2,2-trifluoroacetamide (182 mg, 38% for four steps). (M+H)+=472.

Workup

  1. extractionThe reaction was extracted from 1 M HCl with EtOAc×3
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customammonia gas was bubbled in for 1 min
  6. temperatureto warm to rt
  7. dissolutionThis compound was dissolved in 15 mL THF
  8. stirringstirred for 3 h
  9. customThe reaction was quenched with EtOAc
  10. stirringAfter stirring 30 min
  11. extractionthe reaction was extracted from brine 4× EtOAc
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-47285f5110aa47faa0b89717f95bc1d8
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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