Nonane → tert-Butyl [3-(4-{[(1-adamantylmethyl)amino]carbonyl)-5-chloropyridin-2-yl)propyl](3-{[tert-butyl(dimethyl)silyl]oxy}propyl)carbamate

HRID 1247586Notes

Reaction equation

HRID 1247586 reaction equation
[CH2:1]([N:4]([CH2:12][CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:2]=[CH2:3].CCCCCCCCC.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:40]12([CH2:50][NH:51][C:52](=[O:61])[C:53]3[C:58]([Cl:59])=[CH:57][N:56]=[C:55](Cl)[CH:54]=3)[CH2:49][CH:44]3[CH2:45][CH:46]([CH2:48][CH:42]([CH2:43]3)[CH2:41]1)[CH2:47]2>O1CCCC1.O.CN(C)C=O.[Cl-].[Na+].O.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:7]([O:6][C:5](=[O:11])[N:4]([CH2:1][CH2:2][CH2:3][C:55]1[CH:54]=[C:53]([C:52]([NH:51][CH2:50][C:40]23[CH2:41][CH:42]4[CH2:48][CH:46]([CH2:45][CH:44]([CH2:43]4)[CH2:49]2)[CH2:47]3)=[O:61])[C:58]([Cl:59])=[CH:57][N:56]=1)[CH2:12][CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])([CH3:9])([CH3:10])[CH3:8]

Participants

10

Reactant 4

HCID 8141NonaneHCID 62657Potassium Phosphate, TribasicHCID 11416492N-(1-adamantylmethyl)-2,5-dichloroisonicotinamideHCID 86595927Tert-butyl allyl(3-(tert-butyldimethylsilyloxy)propyl)carbamate

Product 1

HCID 69586523tert-Butyl [3-(4-{[(1-adamantylmethyl)amino]carbonyl)-5-chloropyridin-2-yl)propyl](3-{[tert-butyl(dimethyl)silyl]oxy}propyl)carbamateYield 49.2%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl allyl(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)carbamate (0.50 g) in 9-boroabicyclo[3.3.1]nonane (6.0 ml of a 0.5M solution in tetrahydrofuran) was heated at reflux under nitrogen for 4 hours. The solution was cooled to 0° C. and potassium phosphate (2 ml of a 3M solution in water) was added. The mixture was stirred for 15 minutes and a solution of N-(1-adamantylmethyl)-2,5-dichloroisonicotinamide (0.50 g) (prepared as described in WO 01/94338) and tetrakis(triphenylphosphine)palladium (0) (0.045 g) in anhydrous N,N-dimethylformamide (3 ml) was added. The mixture was heated at 70° C. under nitrogen for 4 hours, diluted with saturated brine (25 ml) and extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica, gel eluting with iso-hexane:ethyl acetate (9:1 to 4:1) to afford the sub-titled compound (0.46 g).

Workup

  1. temperatureat reflux under nitrogen for 4 hours
  2. temperatureThe mixture was heated at 70° C. under nitrogen for 4 hours
  3. extractionextracted into ethyl acetate (3×25 ml)
  4. dry with materialThe combined extracts were dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica, gel
  8. washeluting with iso-hexane:ethyl acetate (9:1 to 4:1)

Sources & evidence

ORD record
ord-140465e27e2b4aac84771e96485ce3b5
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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