3-Isocyanatopyridine → N-((1S,2R,3S,4R)-4-[6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-acetamide

HRID 2382418Notes

Reaction equation

HRID 2382418 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]=[C:21]3[C:17]([N:18]=[CH:19][N:20]3[C@@H:23]3[CH2:27][C@H:26]([NH:28][C:29](=[O:32])[CH2:30][OH:31])[C@@H:25]([OH:33])[C@H:24]3[OH:34])=[C:16]([NH:35][CH2:36][CH:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:15]=2)[CH2:10]1.[N:50]([C:53]1[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=1)=[C:51]=[O:52]>C1COCC1>[C:44]1([CH:37]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:36][NH:35][C:16]2[N:15]=[C:14]([N:11]3[CH2:12][CH2:13][C@@H:9]([NH:8][C:51]([NH:50][C:53]4[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=4)=[O:52])[CH2:10]3)[N:22]=[C:21]3[C:17]=2[N:18]=[CH:19][N:20]3[C@@H:23]2[CH2:27][C@H:26]([NH:28][C:29](=[O:32])[CH2:30][OH:31])[C@@H:25]([OH:33])[C@H:24]2[OH:34])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

4

Reactant 2

HCID 27604933-IsocyanatopyridineHCID 42632577N-{(1S,2R,3S,4R)-4-[2-((R)-3-Amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide trifluoroacetate

Product 1

HCID 66630687N-((1S,2R,3S,4R)-4-[6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide trifluoroacetate (0.2 g, 0.28 mmol) in dry THF (10 ml) is treated with TEA (113 mg, 1.12 mmol) followed by 3-isocyanato-pyridine (38 mg, 0.31 mmol). The reaction mixture is heated at 50° C. overnight. The solvent is removed in vacuo and purification by reverse phase column chromatography (Isolute™ C18, 10-50% acetonitrile in water—0.1% TFA) affords the product. The product is further purified by dissolving in MeOH and treating with saturated sodium bicarbonate solution. The mixture is passed through a pre-washed (400 ml MeOH followed by 400 ml water) eluting with 0.5% ammonia 880: water (100 ml) followed by water (400 ml) and finally MeOH to afford the title compound. (MH+ 693.4)

Workup

  1. customThe solvent is removed in vacuo and purification by reverse phase column chromatography (Isolute™ C18, 10-50% acetonitrile in water—0.1% TFA)
  2. customaffords the product
  3. customThe product is further purified
  4. dissolutionby dissolving in MeOH
  5. additiontreating with saturated sodium bicarbonate solution
  6. washa pre-washed (400 ml MeOH followed by 400 ml water)
  7. washeluting with 0.5% ammonia 880

Sources & evidence

ORD record
ord-9ab564532b354107b6a0b03e69c47e5a
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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