Trifluoroacetic acid → N-(1-hydroxy-2-methylpropan-2-yl)-2-(1-methyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 522979Notes

Reaction equation

HRID 522979 reaction equation
[OH:1][CH2:2][C:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([NH:18][C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])([CH3:5])[CH3:4].FC(F)(F)C(O)=O>ClCCl.CO.[OH-].[NH4+]>[OH:1][CH2:2][C:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([NH:18][C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])([CH3:5])[CH3:4]

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90041492N-(1-hydroxy-2-methylpropan-2-yl)-2-(1-methyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 73295611N-(1-hydroxy-2-methylpropan-2-yl)-2-(1-methyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 64.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of N-(1-hydroxy-2-methylpropan-2-yl)-2-(1-methyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (26 mg, 56.6 mol) in dichloromethane (1 mL) was added trifluoroacetic acid (129 mg, 87.2 μL, 1.13 mmol) and the mixture stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue obtained diluted with dichloromethane (1 mL), methanol (0.5 mL) and ammonium hydroxide (0.15 mL) and stirred at room temperature for 2 h. The mixture was concentrated and triturated with water. The solid was collected by filtration and washed with water and ether to give N-(1-hydroxy-2-methylpropan-2-yl)-2-(1-methyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (12 mg, 36.4 mol, 64%) as a brown solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.19 (s, 1H), 9.16 (s, 1H), 8.01 (s, 1H), 7.91 (d, J=3.0, 1 H), 7.86 (s, 1H), 7.70 (s, 1H), 7.49 (s, 1H), 5.15 (t, J=5.7, 1 H), 3.82 (s, 3H), 3.57 (d, J=5.9, 2 H), 1.37 (s, 9H); MS (EI/CI) m/z: 330.2 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue obtained
  3. stirringstirred at room temperature for 2 h
  4. concentrationThe mixture was concentrated
  5. customtriturated with water
  6. filtrationThe solid was collected by filtration
  7. washwashed with water and ether

Sources & evidence

ORD record
ord-aef89f2f94094a039210fd685905dcd4
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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