Diisopropylethylamine → HCID 10475938, compound

HRID 1984282Notes

Reaction equation

HRID 1984282 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:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][C@@H:32]([CH2:38][CH3:39])[CH:33]([OH:37])[CH:34]([CH3:36])[CH3:35]>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][C@@H:32]([CH2:38][CH3:39])[CH:33]([OH:37])[CH:34]([CH3:36])[CH3:35])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11565460HCID 11565460, compoundHCID 57714157(3RS,4S)-4-Amino-2-methyl-hexan-3-ol

Product 1

HCID 10475938HCID 10475938, compound

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-2-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 (0.20 mL, 11 eq, 1.14 mmol) followed by (3RS,4S)-4-amino-2-methyl-hexan-3-ol (28 mg, 2.0 eq, 0.21 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 brine/water (1:1, 100 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: 5.7 mg (14%). (50% de 4S,3R: 50% de 4S,3S). 1H-NMR (d-CDCl3, 250 MHz): δ 0.90-1.06 (m, 9H, —NHCH(CH2CH3)CH(CH3)2OH), 1.57 (d, 6H, J=6.79 Hz, —CH(CH3)2), 1.64-1.93 (m, 4H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.24-3.37 (m, 1H, —NHCH(CH2CH3) CH(CH (CH3)2)OH), 3.80-3.95 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.57-4.71 (m, 1H, —CH(CH3)2), 4.84-4.96 (m, 2H, —HNCH2-Pyr), 5.13-5.24 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 6.65-6.80 (m, 1H, —HNCH2-Pyr), 7.12-7.23 (m, 1H, Pyr-H), 7.30-7.40 (m, 1H, Pyr-H), 7.56 (s, 1H, —N═CH—N—), 7.59-7.74 (m, 1H, Pyr-H), 8.61 (d, 1H, J=4.42 Hz, Pyr-H). FABMS m/z (relative intensity): 398 ([M+H]+, 100), 324 (55). Accurate Mass (M+H): Actual: 398.2668, Measured: 398.2654.

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 brine/water (1:1, 100 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. customdried (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-7e72fe432650448c872c3e7a657cbae9
Source dataset
uspto-grants-2009_06
Patent number
US07544689B2

Reaction notes

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