Diisopropylethylamine → HCID 12111412, 화합물

HRID 729587노트

반응식

HRID 729587 반응식
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(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:17]=[N:18][CH:19]=[CH:20][CH:21]=1)([CH3:13])[CH3:12]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amineHCID 57714157(3RS,4S)-4-Amino-2-methyl-hexan-3-ol

생성물 1

HCID 12111412HCID 12111412, 화합물

시약·촉매·용매 1

HCID 20476217n-BuOH DMSO용매

실험 절차

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 (0.20 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: 4.3 mg (10%). 50% de 4S,3R: 50% de 4S,3S). 1H-NMR (d-CDCl3, 250 MHz): δ 0.91-1.05 (m, 9H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 1.57 (d, 6H, J=6.95 Hz, —CH(CH3)2), 1.60-1.95 (m, 4H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.23-3.33 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.84-4.04 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.56-4.70 (m, 1H, —CH(CH3)2), 4.77-4.95 (m, 2H, —HNCH2-Pyr), 5.26-5.43+6.27-6.50 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 7.23-7.37 (m, 3H, 2×Pyr-H & —N═CH—N—), 7.51-7.63 (m, 1H, Pyr-H), 7.73 (d, 1H, J=7.74 Hz, Pyr-H), 8.48-8.76 (m, 1H, HNCH2-Pyr). FABMS m/z (relative intensity): 398 ([M+H]+, 100), 324 (60). Accurate Mass (M+H): Actual: 398.2668, Measured: 398.2654.

후처리

  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. 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)

출처 및 근거

ORD 기록
ord-3057524ea8d74eabaea6778fa6bcc325
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582642B2

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