Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → rac-tert-Butyl 1-(3-{[cyclopent-1-en-1-yl(4-methoxypiperidin-1-yl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

HRID 626451Notes

Reaction equation

HRID 626451 reaction equation
[C:1]1([CH:6]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][CH3:17])[CH2:12][CH2:11]2)[C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[CH:44]=[C:45]([CH:57]=[CH:58][C:59]=1[F:60])[CH2:46][C:47]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:49][CH2:48]1>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[C:1]1([CH:6]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][CH3:17])[CH2:12][CH2:11]2)[C:7]([NH:42][C:43]2[CH:44]=[C:45]([CH:57]=[CH:58][C:59]=2[F:60])[CH2:46][C:47]2([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:48][CH2:49]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136688tert-Butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylateHCID 90014907rac-Cyclopent-1-en-1-yl(4-methoxypiperidin-1-yl)acetic acid

Product 1

HCID 90014967rac-tert-Butyl 1-(3-{[cyclopent-1-en-1-yl(4-methoxypiperidin-1-yl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21954950Dimethylformamide pyridineSolvent

Procedure

30.9 mg (0.13 mmol) of rac-cyclopent-1-en-1-yl(4-methoxypiperidin-1-yl)acetic acid were initially charged in 0.87 ml of DMF/pyridine (3:1), 63.8 mg (0.17 mmol) of HATU were added and the mixture was stirred at RT for 30 min 34.3 mg (0.13 mmol) of tert-butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylate were then added, and the reaction mixture was stirred at RT overnight. The mixture was then diluted with ethyl acetate, washed repeatedly with saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by preparative HPLC (RP18 column; acetonitrile/water gradient with addition of 0.1% TFA, 10:90→95:5; run time 38 min). This gave 20.7 mg (33% of theory) of the title compound.

Workup

  1. additionwere then added
  2. washwashed repeatedly with saturated sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (RP18 column; acetonitrile/water gradient with addition of 0.1% TFA, 10:90→95:5; run time 38 min)

Sources & evidence

ORD record
ord-6ff21bddfdfa49129420820bf6f0ca8d
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

Loading…