Diisopropylethylamine → 1,1-dimethylethyl {(1R)-1-[({6-[(3-methyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}amino)carbonyl]propyl}carbamate

HRID 527578노트

반응식

HRID 527578 반응식
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:48][CH:49]1[C:53]2[C:54]([O:58][C:59]3[N:64]=[CH:63][C:62]([NH2:65])=[CH:61][CH:60]=3)=[CH:55][CH:56]=[CH:57][C:52]=2[CH2:51][O:50]1>CN(C)C=O>[CH3:48][CH:49]1[C:53]2[C:54]([O:58][C:59]3[N:64]=[CH:63][C:62]([NH:65][C:10]([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH3:14])=[O:12])=[CH:61][CH:60]=3)=[CH:55][CH:56]=[CH:57][C:52]=2[CH2:51][O:50]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679606486-[(3-Methyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinamine2회

생성물 1

HCID 679669891,1-dimethylethyl {(1R)-1-[({6-[(3-methyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}amino)carbonyl]propyl}carbamate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

In a 8 ml vial (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (32.2 mg, 0.158 mmol) was dissolved in N,N-dimethylformamide (0.5 ml) to give a colourless solution. DIPEA (0.035 ml, 0.198 mmol) and HATU (60.3 mg, 0.158 mmol) were added. The reaction mixture was stirred at room temperature for 30 minutes. 6-[(3-methyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinamine (Intermediate 100, 32 mg) was dissolved in 1.5 ml of DMF and the obtained solution was added to the reaction mixture. It was shaken at 60° C. After 2 hours, no reaction occurred. Additional 0.5 ml of a solution [obtained dissolving in 0.5 ml of DMF (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (32.2 mg, 0.158 mmol), DIPEA (0.035 mL, 0.198 mmol) and HATU (60.3 mg, 0.158 mmol)] was added to the reaction mixture. It was shaken at 60° C. over weekend. After that time, only traces of the title compound along with the Intermediate 100 was detected. The reaction mixture was evaporated under vacuum using the Vaportec V10 to give the crude product which was purified by silica gel chromatography (Biotage SP1 system, 10 g-SNAP Silica column) with Cyclohexane/EtOAc as eluents (from 3/1 to 1/1 in 10 CV; then 1/1 for 10 CV). The collected fractions afforded 4.9 mg of the title compound mixed with the amino acid and 61 mg of a mixture of starting material (Intermediate 100) and the amino acid.

후처리

  1. customto give a colourless solution
  2. additionthe obtained solution was added to the reaction mixture
  3. stirringIt was shaken at 60° C
  4. waitAfter 2 hours
  5. stirringIt was shaken at 60° C. over weekend

출처 및 근거

ORD 기록
ord-a22c37399533447290b4fc3d838c7383
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

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