Dimethylformamide → HCID 90387270, compound

HRID 1476836Notes

Reaction equation

HRID 1476836 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]2)[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:25]([C:2]1[N:3]=[C:4]([O:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]2)[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)#[N:26]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 90386966HCID 90386966, compound

Product 1

HCID 90387270HCID 90387270, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of (S)-tert-butyl 3-((3-chloroisoquinolin-1-yl)oxy)pyrrolidine-1-carboxylate (4.430 g, 12.70 mmol), zinc cyanide (2.980 g, 25.40 mmol) and Pd(PPh3)4 (1.468 g, 1.27 mmol) in DMF (36.3 mL) was heated at 160° C. for 20 minutes in a microwave reactor. The reaction mixture was filtered, diluted with water (400 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by silica column chromatography to give the title compound as a white-to-pale-yellow solid (3.570 g, 83%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.40 (d, J=13.18 Hz, 9H), 2.23 (d, J=11.23 Hz, 2H), 3.42-3.59 (m, 3H), 3.65-3.75 (m, 1H), 5.68-5.80 (m, 1H), 7.82-7.89 (m, 1H), 7.91-7.98 (m, 1H), 8.06 (d, J=8.79 Hz, 1H), 8.21-8.30 (m, 2H); ESI-MS m/z [M+H-tert-butyl]+ 284.6.

Workup

  1. filtrationThe reaction mixture was filtered
  2. additiondiluted with water (400 mL)
  3. extractionextracted with EtOAc (2×100 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica column chromatography

Sources & evidence

ORD record
ord-80ac70f24a33469bae3439944dc14ce7
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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