Diisopropylethylamine → HCID 89402035, compound

HRID 1487023Notes

Reaction equation

HRID 1487023 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:14](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[CH:15]=[CH:16][CH:17]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[F:26][C:27]1([F:31])[CH2:30][NH:29][CH2:28]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([C:13]2[N:14](/[CH:18]=[CH:19]\[C:20]([N:29]3[CH2:30][C:27]([F:31])([F:26])[CH2:28]3)=[O:21])[CH:15]=[CH:16][CH:17]=2)[CH:4]=[C:3]([C:2]([F:23])([F:1])[F:24])[CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 89402029HCID 89402029, compound

Product 1

HCID 89402035HCID 89402035, compoundYield 6.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL 3-neck round-bottomed flask was charged with a solution of (Z)-3-(2-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrrol-1-yl)acrylic acid (0.15 g, 0.429 mmol) in DCM (10 mL) and cooled to 0° C. and 3,3-difluoroazetidine hydrochloride (0.052 g, 0.558 mmol) was added dropwise. T3P (50% in EtOAc) (0.163 g, 0.514 mmol) was added dropwise followed by DIPEA (0.11 g, 0.858 mmol) and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was concentrated under reduced pressure to afford 0.2 g of crude product which was purified by column chromatography (60/120 silica gel, 0-3% ethylacetate:n-hexane gradient) to afford 0.01 g of (Z)-3-(2-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrrol-1-yl)-1-(3,3-difluoro azetidin-1-yl)prop-2-en-1-one (Yield 6.6%). 1H NMR (400 MHz, CDCl3, ppm) δ=4.307-4.425 (m, 4H); 5.523-5.443 (d, J=10 Hz, 1H); 6.387-6.404 (t, 1H); 6.500-6.509 (t, 1H); 6.765-6.790 (d, J=10 Hz, 1H); 7.704-7.715 (t, 1H); 7.811-7.845 (m, 3H). LCMS calcd for: C18H13F8N2O [M+H]+435.29. found 425.49 (retention time 3.292 min).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto afford 0.2 g of crude product which
  3. customwas purified by column chromatography (60/120 silica gel, 0-3% ethylacetate:n-hexane gradient)

Sources & evidence

ORD record
ord-2fde3f28b32642cebb66b999d5de2a50
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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