Trifluoroacetic acid → 3-((3S,9aR)-8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)octahydro-1H-pyrazino[1,2-a]pyrazin-3-yl)-6-fluoro-2-methylbenzonitrile

HRID 1502181Notes

Reaction equation

HRID 1502181 reaction equation
[N:1]1([C:6]2[N:11]=[CH:10][C:9]([CH2:12][C:13]([N:15]3[CH2:41][CH2:40][N:18]4[CH2:19][C@H:20]([C:30]5[CH:35]=[CH:34][C:33]([F:36])=[C:32]([C:37]#[N:38])[C:31]=5[CH3:39])[N:21](C(OC(C)(C)C)=O)[CH2:22][C@@H:17]4[CH2:16]3)=[O:14])=[CH:8][N:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.C1(SC)C=CC=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[N:1]1([C:6]2[N:11]=[CH:10][C:9]([CH2:12][C:13]([N:15]3[CH2:41][CH2:40][N:18]4[CH2:19][C@H:20]([C:30]5[C:31]([CH3:39])=[C:32]([C:33]([F:36])=[CH:34][CH:35]=5)[C:37]#[N:38])[NH:21][CH2:22][C@@H:17]4[CH2:16]3)=[O:14])=[CH:8][N:7]=2)[CH:5]=[N:4][N:3]=[N:2]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 89619169(3S,9aS)-tert-butyl 8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

Product 1

HCID 896335353-((3S,9aR)-8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)octahydro-1H-pyrazino[1,2-a]pyrazin-3-yl)-6-fluoro-2-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of (3S,9aS)-tert-butyl 8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate (60 mg, 0.107 mmol) in methylene chloride (2 mL) was added thioanisole (50.5 μl, 0.427 mmol) and trifluoroacetic acid (3287 μl, 42.7 mmol), the resulting solution was stirred at rt for 1 h. After removing the volatile, the residue was participated between methylene chloride (100 mL) and 1N sodium hydroxide (50 mL), the alkaline phase was extracted with methylene chloride, the combined methylene chloride phase was dried over sodium sulphate, concentrated and the residue was purified on TLC using 10% methanol/methylene chloride to give title compound. 1H NMR (500 MHz, CDCl3) δ 9.60 (s, 1H), 8.81-8.80 (two singlets, 2H), 8.43-8.40 (m, 1H), 7.06-7.02 (m, 1H), 5.33 (s, 2H), 4.574-4.40 (m, 1H), 4.23-4.22 (m, 1H), 3.89-3.80 (m, 2H), 3.70-3.54 (m, 1H), 3.26-3.14 (m, 2H), 3.03-2.90 (m, 2H), 2.80-2.67 (m, 2H), 2.64-2.63 (two singlets, 3H), 2.59-2.38 (m, 2H); LC/MS: [(M+23)]+=485.13; [(M+1-28)]+=435.20.

Workup

  1. customAfter removing the volatile, the residue
  2. extractionthe alkaline phase was extracted with methylene chloride
  3. dry with materialthe combined methylene chloride phase was dried over sodium sulphate
  4. concentrationconcentrated
  5. customthe residue was purified on TLC

Sources & evidence

ORD record
ord-0dbaa5cc58854593921fb4926fd5c8f0
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

Loading…