Diisopropylethylamine → (3RS,4S)-4-{9-Isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-hexan-3-ol

HRID 729585ノート

反応式

HRID 729585 の反応式
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]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][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]([CH2:37][CH3:38])[CH:33]([OH:36])[CH2:34][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]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amineHCID 57714156(3RS,4S)-4-amino-hexan-3-ol

生成物 1

HCID 12111410(3RS,4S)-4-{9-Isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-hexan-3-ol

試薬・触媒・溶媒 1

HCID 20476217n-BuOH DMSO溶媒

実験手順

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (20 mg, 1 eq, 0.07 mmol) in n-BuOH/DMSO (3.75 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.18 mL, 15 eq, 1.03 mmol) followed by (3RS,4S)-4-amino-hexan-3-ol (110 mg, 13 eq, 0.94 mmol). The reaction mixture was placed in a preheated oil bath at 140° 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: 15.5 mg (58%). (57% de 4S,3R: 43% de 4S,3S). 1H-NMR (d-CDCl3, 250 MHz): δ 0.84-1.09 (m, 6H, —NHCH(CH2CH3) CH(CH2CH3)OH), 1.57 (d, 6H, J=6.48 Hz, & —CH(CH3)2), 1.42-1.64 (m, 4H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.45 (d, 1H, J=6.31 Hz, OH), 3.55-3.71 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.88-4.03 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 4.56-4.74 (m, 1H, —CH(CH3)2), 4.78-4.99 (m, 2H, —HNCH2-Pyr), 5.20-5.29 & 6.20-6.39 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 7.20-7.36 (m, 3H, 2×Pyr-H+ —N═CH—N—), 7.49-7.60 (m, 1H, Pyr-H), 7.72 (d, 1H, J=7.82 Hz, Pyr-H), 8.71 (m, 1H, HNCH2-Pyr). FABMS m/z (relative intensity): 384 ([M+H]+, 100), 324 (35), 297 (15). Accurate Mass (M+H): Actual: 384.2512, Measured: 384.2500.

後処理

  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 (2×25 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)

出典と根拠

ORDレコード
ord-c5a60c3d6a7344b6be6cd158bf17e30d
出典データセット
uspto-grants-2009_09
特許番号
US07582642B2

反応ノート

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