Trifluoroacetic acid → HCID 86679005, compound

HRID 2203366Notes

Reaction equation

HRID 2203366 reaction equation
[NH2:1][C:2]1[C:3]2[CH:29]([CH3:30])[C:28](=[O:31])[N:27](C(OC(C)(C)C)=O)[C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[N:9]=2)[N:7]=1.[C:39]([N:43]=C(N(C)C)N(C)C)(C)(C)[CH3:40].BrCC#N.[NH4+].[Cl-].C(O)(C(F)(F)F)=O>C1COCC1>[NH2:1][C:2]1[C:3]2[C:29]([CH2:40][C:39]#[N:43])([CH3:30])[C:28](=[O:31])[NH:27][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:25])([F:26])[C:21]([F:24])([F:23])[F:22])[N:9]=2)[N:7]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 86679003HCID 86679003, compound

Product 1

HCID 86679005HCID 86679005, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the intermediate from Step B above (102 mg, 0.182 mmol) stirred in THF (3566 μl) was added 2-tert-butyl-1,1,3,3-tetramethylguanidine (34.2 μl, 0.182 mmol) followed by 2-bromoacetonitrile (19.02 μl, 0.273 mmol). After stirring for 5 minutes at room temperature, saturated aqueous NH4Cl was added. The reaction mixture reaction was then partitioned between EtOAc and water. The organic layer was dried (sodium sulfate), filtered and concentrated in vacuo. The crude material was taken up in DCM (1 mL) and TFA (280 μl, 3.64 mmol) was added. After 3 hours the reaction was quenched with aq. NaHCO3 and partitioned between water and EtOAc. The organic layer was dried, concentrated in vacuo and purified by silica gel column chromatography using a hexanes/EtOAc gradient to afford the product as a white solid. Chiral separation using SFC provided both enantiomers of the title compound. 1H NMR (500 MHz, CHCl3-d): δ 8.45 (d, J=8.72 Hz, 1H); 7.43 (s, 1H); 7.18 (dd, J=8.75, 1.62 Hz, 1H); 5.48 (s, 2H); 4.71 (t, J=7.69 Hz, 2H); 2.99 (d, J=16.98 Hz, 1H); 2.81-2.68 (m, 2H); 2.67 (d, J=16.98 Hz, 1H); 1.68 (s, 3H). m/z=500.0 (M+H).

Workup

  1. customThe reaction mixture reaction
  2. customwas then partitioned between EtOAc and water
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customAfter 3 hours the reaction was quenched with aq. NaHCO3
  7. custompartitioned between water and EtOAc
  8. customThe organic layer was dried
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-76af0288fda042e1b110b7ae99345c60
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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