1,2-Dichloroethane → HCID 70975806, compound

HRID 535487Notes

Reaction equation

HRID 535487 reaction equation
[NH2:1][N:2]1[N:11]=[C:10]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:17].[F:18][C:19]1[CH:20]=[C:21]([CH2:26][C:27](O)=[O:28])[CH:22]=[C:23]([F:25])[CH:24]=1.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[F:18][C:19]1[CH:20]=[C:21]([CH2:26][C:27]([NH:1][N:2]2[N:11]=[C:10]([C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]2=[O:17])=[O:28])[CH:22]=[C:23]([F:25])[CH:24]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 1454243,5-Difluorophenylacetic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 70975803HCID 70975803, compound

Product 1

HCID 70975806HCID 70975806, compoundYield 19.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

The product from Example 10B (60 mg, 0.25 mmol), (3,5-difluorophenyl)acetic acid (51 mg, 0.30 mmol), 1-hydroxybenzotriazole hydrate (HOBT, 76 mg, 0.49 mmol), EDC (95 mg, 0.49 mmol), and DMAP (3.0 mg, 0.025 mmol) were combined in pyridine (3 mL). The mixture was stirred at room temperature for 12 hours. The mixture was concentrated to dryness. The residue was dissolved in EtOAc and washed with NaHCO3, dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative HPLC [Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min linear gradient 95-10% A] to afford 19 mg (19%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.79 (s, 1H), 8.42 (ddd, J=7.8, 1.5, 0.6 Hz, 1H), 8.18 (ddd, J=8.1, 1.3, 0.6 Hz, 1H), 8.05 (ddd, J=8.0, 7.3, 1.5 Hz, 1H), 7.99 (ddd, J=7.9, 7.2, 1.3 Hz, 1H), 7.81 (dd, J=5.1, 1.1 Hz, 1H), 7.66 (dd, J=3.6, 1.1 Hz, 1H), 7.29 (dd, J=5.1, 3.6 Hz, 1H), 7.06-7.22 (m, 3H), 3.78 (s, 2H); MS (APCI) M/Z 398 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with NaHCO3
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC [Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm)
  8. custom0-0.5 min 10% A, 0.5-7.0 min
  9. customlinear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min

Sources & evidence

ORD record
ord-38285969e6fe4b03980266b4fde59d2d
Source dataset
uspto-grants-2014_10
Patent number
US08859549B2

Reaction notes

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