HCID 89404252, compound → HCID 71494739, compound

HRID 1487004Notes

Reaction equation

HRID 1487004 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([N:22]3[CH2:27][CH:26]4[CH:24]([CH:25]4[NH:28]C(=O)OCC4C5C=CC=CC=5C5C4=CC=CC=5)[CH2:23]3)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1>CN(C=O)C>[NH2:28][CH:25]1[CH:24]2[CH:26]1[CH2:27][N:22]([C:20](=[O:21])/[CH:19]=[CH:18]\[N:15]1[CH:16]=[N:17][C:13]([C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:46])[F:47])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=3)=[N:14]1)[CH2:23]2

Participants

3

Reactant 1

HCID 89404252HCID 89404252, compound

Product 1

HCID 71494739HCID 71494739, compoundYield 50.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(Z)-(9H-Fluoren-9-yl)methyl (3-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acryloyl)-3-azabicyclo[3.1.0]hexan-6-yl)carbamate (0.3 g, 1.0 eq.) in was dissolved in DMF (0.75 ml). TEA (0.75 ml) was added dropwise and the reaction mixture was stirred at room temperature for 4 h, quenched with water (10 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford 0.2 g of the crude product, which was purified by chromatography (10% Methanol in DCM) to obtain (Z)-1-(6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)prop-2-en-1-one (0.1 g; 50% yield). 1H NMR (400 MHz, DMSO) δ=9.10 (s, 1H), 8.49 (s, 2H), 8.30 (s, 1H), 7.30-7.32 (d, J=10 Hz, 1H), 6.07-6.09 (d, J=10 Hz, 1H), 3.65-3.68 (d, 1H), 3.48 (s, 1H), 3.35-3.45 (m, 1H), 3.29-3.30 (d, 1H), 2.28 (s, 1H), 1.48-1.49 (m, 2H), 1.22 (s, 1H); LCMS calcd. for C18H16F6N5O [M+H]+ 432.34. found 432.19 at 2.1 min retention time.

Workup

  1. customquenched with water (10 mL)
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers was washed with brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  7. customto afford 0.2 g of the crude product, which
  8. customwas purified by chromatography (10% Methanol in DCM)

Sources & evidence

ORD record
ord-f92c3bd8e2f044ca9685ebce3ab35ea0
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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