Tetrahydrofuran → 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)-N-(2-piperidin-1-ylethyl)purine-2-carboxamide

HRID 2184257Notes

Reaction equation

HRID 2184257 reaction equation
[C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17](I)[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][N:14]3[C@H:20]2[C@H:24]([OH:25])[C@H:23]([OH:26])[C@@H:22]([CH2:27][OH:28])[O:21]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.[O:44]1CCC[CH2:45]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:25][C@@H:24]1[C@H:23]([OH:26])[C@@H:22]([CH2:27][OH:28])[O:21][C@H:20]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([C:45]([NH:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1)=[O:44])=[N:18][C:10]=2[NH:9][CH2:8][CH:7]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 33944N-(2-Aminoethyl)piperidineHCID 57135198HCID 57135198, compound

Product 1

HCID 98088349-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)-N-(2-piperidin-1-ylethyl)purine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

A solution of (2R,3R,4S,5R)-2-{6-[(2,2-diphenylethyl)amino]-2-iodo-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydro-3,4-furandiol (59, 8.7 mmol) (Preparation 2), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (1:1 complex with dichloromethane) (0.7 g, 0.9 mmol) and 1-(2-aminoethyl)piperidine (3.49, 26.5 mmol) in anhydrous tetrahydrofuran (250 ml) was heated at 60° C., under a carbon monoxide atmosphere at 345 kPa (50 psi) in a sealed vessel for 24 hours. The mixture was cooled, filtered through a pad of Arbocel (trade mark) and the filtrate diluted with tetrahydrofuran (150 ml) and ethyl acetate (400 ml). The resulting solution was washed with water (3×300 ml) and the organic phase extracted with 2 M aqueous hydrochloric acid solution (50 ml). The acidic aqueous phase was washed with ethyl acetate (20 ml) then the pH adjusted to >7 by addition of 0.88 aqueous ammonia solution. Ethyl acetate (100 ml) was added and the mixture stirred for 10 minutes after which time a white solid formed. This solid was filtered, washed sequentially with water and ethyl acetate and dried at 70° C. under reduced pressure to yield the title compound as a white solid (2.8 g).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered through a pad of Arbocel (trade mark)
  3. additionthe filtrate diluted with tetrahydrofuran (150 ml) and ethyl acetate (400 ml)
  4. washThe resulting solution was washed with water (3×300 ml)
  5. extractionthe organic phase extracted with 2 M aqueous hydrochloric acid solution (50 ml)
  6. washThe acidic aqueous phase was washed with ethyl acetate (20 ml)
  7. additionthe pH adjusted to >7 by addition of 0.88 aqueous ammonia solution
  8. additionEthyl acetate (100 ml) was added
  9. customformed
  10. filtrationThis solid was filtered
  11. washwashed sequentially with water and ethyl acetate
  12. customdried at 70° C. under reduced pressure

Sources & evidence

ORD record
ord-f169a31d3f3b45dfa530ffc754d10f30
Source dataset
uspto-grants-2005_05
Patent number
US06900309B1

Reaction notes

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