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(3,4-dihydroisoquinolin-2(1H)-yl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

HRID 626452Notes

Reaction equation

HRID 626452 reaction equation
[C:1]1([CH:6]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11]2)[C:7](O)=[O:8])[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.[NH2:44][C:45]1[CH:46]=[C:47]([CH:59]=[CH:60][C:61]=1[F:62])[CH2:48][C:49]1([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:51][CH2:50]1>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[C:1]1([CH:6]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11]2)[C:7]([NH:44][C:45]2[CH:46]=[C:47]([CH:59]=[CH:60][C:61]=2[F:62])[CH2:48][C:49]2([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:50][CH2:51]2)=[O:8])[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 118106377rac-Cyclopent-1-en-1-yl(3,4-dihydroisoquinolin-2(1H)-yl)acetic acid

Product 1

HCID 118106768rac-tert-Butyl 1-(3-{[cyclopent-1-en-1-yl(3,4-dihydroisoquinolin-2(1H)-yl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21954950Dimethylformamide pyridineSolvent

Procedure

100 mg (0.39 mmol) of rac-cyclopent-1-en-1-yl(3,4-dihydroisoquinolin-2(1H)-yl)acetic acid were initially charged in 2.6 ml of DMF/pyridine (3:1), 192 mg (0.51 mmol) of HATU were added and the mixture was stirred at RT for 30 min. 103 mg (0.39 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 purified directly by preparative HPLC (RP18 column; acetonitrile/water gradient with addition of 0.1% TFA, 10:90→95:5; run time 38 min). The product obtained in this manner was taken up in ethyl acetate and washed repeatedly with 1 N hydrochloric acid. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. This gave 103 mg (purity 72%, 37% of theory) of the title compound which was reacted without further purification.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. customThe mixture was then purified directly by preparative HPLC (RP18 column; acetonitrile/water gradient with addition of 0.1% TFA, 10:90→95:5; run time 38 min)
  3. customThe product obtained in this manner
  4. washwashed repeatedly with 1 N hydrochloric acid
  5. dry with materialThe organic phase was dried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThis gave 103 mg (purity 72%, 37% of theory) of the title compound which was reacted without further purification

Sources & evidence

ORD record
ord-f55d7f75fcc743ca87189a9842651685
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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