Dimethylformamide → HCID 59730065, compound

HRID 130940Notes

Reaction equation

HRID 130940 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:24][N:25](C)[CH:26]=[O:27].ClC1[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=CN=1>[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[O:27][C:26]2[CH:38]=[CH:37][C:33]([C:34](=[O:35])[NH2:36])=[CH:24][N:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 804566-ChloronicotinamideHCID 15112489tert-Butyl 3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59730065HCID 59730065, compound

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Combine 5-hydroxy, 3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (2.0 g, 8 mmol), cesium carbonate (5.2 g, 16 mmol) and N,N-dimethylformamide (60 mL), stir at room temperature for 30 minutes. Add 6-chloronicotinamide (1.2 g, 8 mmol) and heat at 100° C. for 2 days. Cool to room temperature, dilute with brine, and then extract with ethyl acetate (3×150 mL). Dry the ethyl acetate extracts with sodium chloride/magnesium sulfate, filter, then concentrate on a rotary evaporator to yield 3 g of the crude product. The crude product is purified by flash column chromatography on silica gel eluting with 0.5% conc. ammonium hydroxide/5% ethanol in chloroform to yield 5-(5-carbamoyl-pyridin-2-yloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (2.1 g, 5.7 mmol): 1H NMR (DMSO-d6, 300.00 MHz): 8.54 (s, 1H); 8.30-8.23 (m, 1H); 8.02-7.93 (m, 1H); 7.48 (s, 1H); 7.23 (d, 1H); 7.09-6.95 (m, 1H); 4.54 (s, 2H); 3.48-3.36 (m, 4H); 2.87-2.71 (m, 2H); 1.39 (s, 9H).

Workup

  1. extractionextract with ethyl acetate (3×150 mL)
  2. dry with materialDry the ethyl acetate
  3. filtrationfilter
  4. concentrationconcentrate on a rotary evaporator
  5. customto yield 3 g of the crude product
  6. customThe crude product is purified by flash column chromatography on silica gel eluting with 0.5% conc. ammonium hydroxide/5% ethanol in chloroform

Sources & evidence

ORD record
ord-f0a1b4acff7c4195866ea8657c9ae10b
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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