Diisopropylethylamine → HCID 69301816, compound

HRID 729582Notes

Reaction equation

HRID 729582 reaction equation
F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1.CCN([CH:28]([CH3:30])[CH3:29])C(C)C.[NH2:31][C@H:32](CC)[C@@H:33]([OH:35])C>CCCCO.CS(C)=O>[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:31][CH2:32][CH:33]([OH:35])[CH2:30][CH2:28][CH3:29])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10866272(2S,3R)-3-aminopentan-2-olHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

Product 1

HCID 69301816HCID 69301816, compound

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (30 mg, 1 eq, 0.10 mmol) in n-BuOH/DMSO (2.5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.2 mL, 10.96 eq, 1.14 mmol) followed by (2S,3R)-3-amino-pentan-2-ol (60 mg, 5.5 eq, 0.58 mmol). The reaction mixture was placed in a preheated oil bath at 160° C. and stirred at this temperature for 72 h. 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 water (50 mL), the aqueous phase was extracted with more EtOAc (2×25 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 CHCl3:MeOH (100:0→98:2), to afford the title compound as a white solid. Yield: 22 mg (57%). (80% de 3R,2S: 20% de 3R,2R). 1H-NMR (d-CDCl3, 250 MHz): δ 0.90, 1.05 (2×t, 3H, J=6.95 & 7.42 Hz, —NHCH (CH2CH3)CH(CH3)OH), 1.17 & 1.25 (2×d, 3H, J=6.32 & 6.16 Hz, —NHCH (CH2CH3)CH(CH3)OH) 1.57 (d, 6H, J=6.79 Hz, —CH(CH3)2), 1.77-2.09 (m, 2H, —NHCH(CH2CH3)CH(CH3)OH), 3.91-4.03 (m, 2H, —NHCH(CH2CH3)CH(CH3)OH), 4.58-4.69 (m, 1H, —CH(CH3)2), 4.83-5.00 (m, 3H, —HNCH2-Pyr & OH), 6.16 (m, 1H, —NHCH(CH2CH3)CH(CH3)OH), 7.24-7.33 (m, 3H, 2×Pyr-H & —N═CH—N—), 7.55 (m, 1H, Pyr-H), 7.74 (d, 1H, J=7.42 Hz, Pyr-H), 8.67 (m, 1H, HNCH2-Pyr). FABMS m/z (relative intensity): 370 ([M+H]+, 100), 324 (35), 289 (37), 243 (65), 199 (85). Accurate Mass (M+H): Actual: 370.2355, Measured: 370.2347.

Workup

  1. customThe reaction mixture was placed in a preheated oil bath at 160° C.
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned between EtOAc (50 mL) and water (50 mL)
  4. extractionthe aqueous phase was extracted with more EtOAc (2×25 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 CHCl3:MeOH (100:0→98:2)

Sources & evidence

ORD record
ord-9c1aa49bfce642969449fbe9c92ed8a0
Source dataset
uspto-grants-2009_09
Patent number
US07582642B2

Reaction notes

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