Cyclopropanemethanamine → 1-(Cyclopropylmethyl)-3-(1-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yl)-1H-indazol-6-yl)urea

HRID 515380Notes

Reaction equation

HRID 515380 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[C:34](Cl)(=O)[O:35]C1C=CC([N+]([O-])=O)=CC=1.[CH:47]1([CH2:50][NH2:51])[CH2:49][CH2:48]1>ClCCl>[CH:47]1([CH2:50][NH:51][C:34]([NH:1][C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:19]=[CH:20][C:21]([C:24]([OH:33])([C:25]([F:26])([F:27])[F:28])[C:29]([F:32])([F:31])[F:30])=[CH:22][CH:23]=4)[CH2:13][CH2:12]3)=[CH:4][CH:3]=2)=[O:35])[CH2:49][CH2:48]1

Participants

5

Reactant 3

HCID 75646CyclopropanemethanamineHCID 821294-Nitrophenyl chloroformateHCID 866710002-(4-((4-(6-Amino-1H-indazol-1-yl)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

Product 1

HCID 866710011-(Cyclopropylmethyl)-3-(1-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yl)-1H-indazol-6-yl)ureaYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(4-((4-(6-Amino-1H-indazol-1-yl)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.212 mmol, 0.1 g) and 4-nitrophenyl carbonochloridate (0.212 mmol, 0.043 g) were combined and stirred in dichloromethane (2 mL) for 1 hour. Cyclopropylmethanamine (0.423 mmol, 0.037 mL, 0.030 g) was added and the reaction stirred at room temperature for 2 hours. The organic was washed with water and dried over sodium sulfate. The solvent was removed and the resulting residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 6% methanol/dichloromethane) to afford the title compound (93 mg). MS (ESI) m/z 570.0 [M+H]+

Workup

  1. washThe organic was washed with water
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed
  4. customthe resulting residue was purified by silica chromatography (
  5. washeluting with a solvent gradient from dichloromethane to 6% methanol/dichloromethane)

Sources & evidence

ORD record
ord-cc2af130838d41e79e6e16afafc9a829
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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