Diisopropylethylamine → (3RS,4R)-4-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-hexan-3-ol

HRID 1432398Notes

Reaction equation

HRID 1432398 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.CCN(C(C)C)C(C)C.[NH2:31][C@H:32]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][CH3:35].C(Cl)Cl.CCOCC.CO>CCCCO.CS(C)=O>[CH2:1]([NH:8][C:9]1[N:17]=[C:16]([NH:31][C@H:32]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][CH3:35])[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

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 17954009Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amineHCID 22565053DCM ether MeOHHCID 57714162(3RS,4R)-4-amino-hexan-3-ol

Product 1

HCID 10177964(3RS,4R)-4-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-hexan-3-ol

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine (40 mg, 1 eq, 0.14 mmol) in n-BuOH/DMSO (3.75 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.24 mL, 9.8 eq, 1.38 mmol) followed by (3RS,4R)-4-amino-hexan-3-ol (110 mg, 6.7 eq, 0.93 mmol). The reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h, when TLC DCM:ether:MeOH (55:40:5) indicated that the reaction had gone to completion The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between EtOAc (50 mL) and brine/water (1:1, 100 mL), the aqueous phase was extracted with more EtOAc (2×50 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 hexane:ether:MeOH (50:50:0→50:50:2) to afford the title compound as a white solid; Yield: 31 mg (58%).(57% de 4R,3S: 43% de 4R,3R). 1H-NMR (d-CDCl3, 250 MHz): δ 0.92-1.08 (m, 6H, —NHCH(CH2CH3)CH(CH2CH3)OH), 1.56 (d, 6H, J=6.79 Hz, +—CH(CH3)2), 1.44-1.69 (m, 4H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.45 (d, 1H, J=6.32 Hz, OH) 3.56-3.70 (m, 1H, —NHCH(CH2CH3) CH(CH2CH3)OH), 3.91-4.06 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 4.58-4.69 (m, 1H, —CH(CH3)2), 4.73-5.01 (m, 2H, —HNCH2-Bz), 5.16-5.32+6.01-6.22 (2×m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 7.22-7.43 (m, 6H, 5×Bz-H+HNCH2-Bz), 7.52 (s, 1H, —N═CH—N). FABMS m/z (relative intensity): 383 ([M+H]+, 100), 323 (55), 296 (21). Accurate Mass (M+H): Actual: 383.2559, Measured: 383.2542.

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 EtOAc (50 mL) and brine/water (1:1, 100 mL)
  4. extractionthe aqueous phase was extracted with more EtOAc (2×50 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 hexane:ether:MeOH (50:50:0→50:50:2)

Sources & evidence

ORD record
ord-15e6dcd6322e4e96a554330f582ba35f
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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