Dimethylacetamide → HCID 71509514, compound

HRID 717539Notes

Reaction equation

HRID 717539 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[C:10]([NH:13]C(NC3C=CC=CC=3)=O)[CH:11]=[CH:12][C:6]=2[N:5]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:24]=2)[CH2:3]1.C[C:39]([N:41](C)C)=O>O.[Zn].[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:13][C:10]1[CH:11]=[CH:12][C:6]2[N:5]=[C:4]([C:23]3[CH:24]=[C:25]([CH:26]=[CH:27][CH:28]=3)[C:39]#[N:41])[CH2:3][C:2](=[O:1])[NH:8][C:7]=2[CH:9]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 71289637HCID 71289637, compound

Product 1

HCID 71509514HCID 71509514, compoundYield 62%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of compound 1 (Example 19, Step 2; 1.0 g, 3.03 mmol) in DMA (20 mL) were added Zn-powder (39.5 mg, 0.60 mmol), Zn(CN)2 (533 mg, 4.51 mmol) and xanthophos (630 mg, 1.12 mmol) at RT under N2 atmosphere. The reaction mixture was degassed with argon for 15 min and then Pd2(dba)3 (556 mg, 0.60 mmol) was added and again degassed for another 15 min. The resulting reaction mixture was heated to 110° C. and stirred for 12 h; progress of the reaction was monitored by TLC. The reaction mixture was cooled to RT; diluted with water (20 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude. The crude material was purified by silica gel column chromatography eluting with 70% EtOAc/Hexane to afford compound 2 (520 mg, 62%). 1H NMR (400 MHz, DMSO-d6): δ 10.34 (bs, 1H), 8.36 (s, 1H), 8.29 (d, J=8.0 Hz, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.70 (t, J=7.6 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 6.53-6.50 (m, 1H), 6.32 (d, J=2.4 Hz, 1H), 5.50 (s, 2H), 3.47 (s, 2H). MS (ESI): m/z 277 [M+1]+

Workup

  1. customThe reaction mixture was degassed with argon for 15 min
  2. customagain degassed for another 15 min
  3. customThe resulting reaction mixture
  4. temperatureThe reaction mixture was cooled to RT
  5. extractionextracted with EtOAc (2×20 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude material was purified by silica gel column chromatography
  10. washeluting with 70% EtOAc/Hexane

Sources & evidence

ORD record
ord-ae8260334af04a26b8021737a79819bd
Source dataset
uspto-grants-2015_11
Patent number
US09193710B2

Reaction notes

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