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Methanol → (2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid

HRID 272224
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HRID 272224 반응식
C([O:3][P:4]([CH2:9][CH:10]([NH:12][C:13](=[O:35])[C:14]1[CH:19]=[CH:18][C:17]([N:20]([CH2:22][C:23]2[N:24]=[C:25]3[C:30](=[N:31][CH:32]=2)[N:29]=[C:28]([NH2:33])[N:27]=[C:26]3[NH2:34])[CH3:21])=[CH:16][CH:15]=1)[CH3:11])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.O.CO>CN(C=O)C>[NH2:33][C:28]1[N:27]=[C:26]([NH2:34])[C:25]2[C:30](=[N:31][CH:32]=[C:23]([CH2:22][N:20]([CH3:21])[C:17]3[CH:16]=[CH:15][C:14]([C:13]([NH:12][CH:10]([CH3:11])[CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:35])=[CH:19][CH:18]=3)[N:24]=2)[N:29]=1
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참가 물질

6

반응물 4

HCID 887MethanolHCID 962WaterHCID 76113BromotrimethylsilaneHCID 57496979(2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid diethyl ester

생성물 1

HCID 68537215(2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid수율 38%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

To a solution of crude (2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid diethyl ester post silica column chromatography (32.2 mg, 66.2 μmol) in dry DMF (0.50 mL) was added TMSBr (68.0 μL, 529.6 μmol) at ambient temperature. The solution was then heated at 70° C. for 1.0 hour, when LCMS analysis demonstrated the reaction to be complete. The reaction mixture was allowed to cool to room temperature, and water (60 μL) and methanol (60 μL) were added. The crude reaction mixture was purified by RP HPLC on C18 column using H2O/acetonitrile (2-95%) to provide 11.2 mg (38%) of the desired compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 1.50 (m, 2H), 1.61 (m, 2H), 3.22 (s, 3H), 3.25-3.40 (m, 2H), 4.84 (s, 2H), 6.80 (d, 2H, J=9 Hz), 7.69 (d, 2H, J=9 Hz), 8.20 (br s, 1H), 8.69 (s, 1H). 31P (121.4 MHz, DMSO-d6) δ 26.3. MS (m/z) 447.3 [M−H]−.

후처리

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. customThe crude reaction mixture
  4. customwas purified by RP HPLC on C18 column

출처 및 근거

ORD 기록
ord-8a8ef114f7694e1cb1970c74a53babf1
출처 데이터셋
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07452901B2

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