Dimethyl Sulfoxide → (2S, 3R)-3-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-pentan-2-ol

HRID 1432394Notes

Reaction equation

HRID 1432394 reaction equation
[CH2:1]([NH:8][C:9]1[N:17]=[C:16](F)[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(C)=O.[NH2:26][C@H:27]([CH2:31][CH3:32])[C@@H:28]([OH:30])[CH3:29]>C(Cl)Cl.CCOCC.CO>[CH2:1]([NH:8][C:9]1[N:17]=[C:16]([NH:26][C@H:27]([CH2:31][CH3:32])[C@@H:28]([OH:30])[CH3:29])[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 10866272(2S,3R)-3-aminopentan-2-olHCID 17954009Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine

Product 1

HCID 10155900(2S, 3R)-3-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-pentan-2-olYield 43%

Reagents, catalysts & solvents 1

HCID 22565053DCM ether MeOHSolvent

Procedure

To a stirred solution of benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine (0.20 g, 0.70 mmol) in BunOH/DMSO (5 mL, 4:1) at RT under Ar was added Pri2NEt (1.2 mL, 6.88 mmol) followed by (2S,3R)-3-amino-pentan-2-ol (0.18 g, 1.74 mmol). The reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h, when TLC (55:40:5, CH2Cl2/Et2O/MeOH) indicated that the reaction had gone to completion. The reaction mixture was allowed to cool to RT and the solvent was evaporated in vacuo. The residue was partitioned between CH2Cl2 (100 ML) and H2O (200 mL), the aqueous phase was extracted with more CH2Cl2 (3×50 mL), and the combined organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel eluted with CH2Cl2/Et2O/MeOH (60:40:0→60:40:2) to afford the title compound as a white solid (0.11 g, 43%, 80% de). Mp 42-44° C. 1H-NMR (d6-DMSO, 250 MHz): δ 0.81 (m, 3H, —NHCH(CH2CH3)CH(CH3)OH), 1.02 (d, 3H, J=6.16 Hz, —NHCH(CH2CH3)CH(CH3)OH) 1.45 (m, 8H, —NHCH(CH2CH3)CH(CH3)OH+—CH(CH3)2), 3.62+3.73 (2×m, 1H, —NHCH(CH2CH3)CH(CH3)OH), 4.49-4.63 (m, 4H, —HNCH2-Bz+—NHCH(CH2CH3)CH(CH3)OH+—CH(CH3)2), 5.59+5.90 ([1.8, 2′R/3′S:2′R/3′S], 2×d, 1H, J=9.00+8.85 Hz, —NHCH(CH2CH3)CH(CH3)OH), 7.19-7.37 (m, 5H, Bz), 7.77 (bs, 2H, —N═CH—N—+—HNCH2-Bz). FAB-MS m/z (relative intensity): 369 ([M+H]+, 100), 323 (70), 134 (15). Accurate Mass (M+H): Actual: 369.2403, Measured: 369.2418.

Workup

  1. customThe reaction mixture was placed in a preheated oil bath at 140° C.
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned between CH2Cl2 (100 ML) and H2O (200 mL)
  4. extractionthe aqueous phase was extracted with more CH2Cl2 (3×50 mL)
  5. washthe combined organic phase was washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by gradient column chromatography on silica gel
  9. washeluted with CH2Cl2/Et2O/MeOH (60:40:0→60:40:2)

Sources & evidence

ORD record
ord-3787212bf21c4a448d053f51ab58b811
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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