HCID 71544157, compound → HCID 86680451, compound

HRID 240440Notes

Reaction equation

HRID 240440 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:12]([N:15]2[CH2:20][CH2:19][N:18]3[CH2:21][C@H:22]([O:24][C:25]4[CH:30]=[N:29][C:28]([CH:31]5[CH2:33][CH2:32]5)=[CH:27][N:26]=4)[CH2:23][C@H:17]3[CH2:16]2)(=[O:14])=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Cu][C:35]#[N:36]>CN(C)C=O>[CH:31]1([C:28]2[N:29]=[CH:30][C:25]([O:24][C@H:22]3[CH2:21][N:18]4[CH2:19][CH2:20][N:15]([S:12]([C:4]5[CH:3]=[C:2]([CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=5)[C:35]#[N:36])(=[O:13])=[O:14])[CH2:16][C@@H:17]4[CH2:23]3)=[N:26][CH:27]=2)[CH2:32][CH2:33]1

Participants

4

Reactant 2

HCID 71544157HCID 71544157, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 86680451HCID 86680451, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of the product from Example 64A (30 mg, 0.055 mmol) in N,N-dimethylformamide (0.3 mL) was added copper(I) cyanide (10 mg, 0.11 mmol), and the resulting mixture was stirred at 130° C. for 16 hours. The cooled mixture was partitioned between water and ethyl acetate (3×), and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-60% ethyl acetate in hexanes to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.87-1.00 (m, 4H), 1.74-1.90 (m, 1H), 1.91-2.07 (m, 2H), 2.19 (t, J=10.34 Hz, 1H), 2.34 (dd, J=10.17, 5.09 Hz, 1H), 2.39-2.63 (m, 3H), 2.98-3.10 (m, 1H), 3.66 (dd, J=10.17, 6.78 Hz, 1H), 3.80 (dd, J=10.17, 1.70 Hz, 1H), 3.88-3.99 (m, 1H), 5.24-5.36 (m, 1H), 7.92 (d, J=1.36 Hz, 1H), 8.03 (d, J=1.36 Hz, 1H), 8.11-8.14 (m, J=1.02 Hz, 1H), 8.17-8.26 (m, J=4.07, 1.02 Hz, 2H); MS (ESI) m/z 494.0 (M+H)+.

Workup

  1. customThe cooled mixture was partitioned between water and ethyl acetate (3×)
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-14a14b19383d4e7c899707c73e3e391d
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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