N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-1-(4-methoxybenzyl)-3-methyl-1H-indazol-5-amine → N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-3-methyl-1H-indazol-5-amine

HRID 1039095Notes

Reaction equation

HRID 1039095 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[N:25](CC3C=CC(OC)=CC=3)[N:24]=[C:23]4[CH3:38])[CH2:10][CH2:9]2)=[N:6][CH:7]=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][N:24]=[C:23]4[CH3:38])[CH2:10][CH2:9]2)=[N:4][CH:3]=1

Participants

3

Reactant 1

HCID 67778018N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-1-(4-methoxybenzyl)-3-methyl-1H-indazol-5-amine

Product 1

HCID 178434303N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-3-methyl-1H-indazol-5-amine

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
75 °C

Procedure

N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-1-(4-methoxybenzyl)-3-methyl-1H-indazol-5-amine (22 mg, 0.041 mmol) from step 3 of this example was dissolved in TFA (200 uL) and stirred at 75° C. for 4.5 hours. The volatiles were removed in vacuum. The residue was then dissolved in MeOH, and the volatiles removed in vacuum. The residue was then dissolved in DCM, and the volatiles removed in vacuum. The product was purified by chromatography on KPNH2™ SiO2 (Biotage) eluting with 5% acetone:DCM to give the titled compound. LRMS calc: 410.20; obs: 411.05 (M+1). Compounds reported in Table 8 are prepared by a general procedure analogous to that described in step 3, Example 48 above.

Workup

  1. customThe volatiles were removed in vacuum
  2. dissolutionThe residue was then dissolved in MeOH
  3. customthe volatiles removed in vacuum
  4. dissolutionThe residue was then dissolved in DCM
  5. customthe volatiles removed in vacuum
  6. customThe product was purified by chromatography on KPNH2™ SiO2 (Biotage)
  7. washeluting with 5% acetone

Sources & evidence

ORD record
ord-863bf84a115e4c79af9a9d99710c1846
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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