Diisopropylethylamine → N-(2-amino-4-(tert-butyl)phenyl)-2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetamide

HRID 2040632노트

반응식

HRID 2040632 반응식
[CH3:1][O:2][C:3]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH3:36])[CH:28]4[CH2:31][CH:30]([CH2:32][C:33]([OH:35])=O)[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.[C:43]([C:47]1[CH:48]=[C:49]([NH2:54])[C:50]([NH2:53])=[CH:51][CH:52]=1)([CH3:46])([CH3:45])[CH3:44].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN(C)C=O>[NH2:54][C:49]1[CH:48]=[C:47]([C:43]([CH3:45])([CH3:44])[CH3:46])[CH:52]=[CH:51][C:50]=1[NH:53][C:33](=[O:35])[CH2:32][CH:30]1[CH2:29][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:25])([CH3:24])[O:23]3)[C@H:16]([N:13]3[C:9]4[N:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]5[CH:37]=[CH:38][C:39]([O:41][CH3:42])=[CH:40][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[O:17]2)[CH3:36])[CH2:31]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 4327084-Tert-butylbenzene-1,2-diamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 677748662-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetic acid

생성물 1

HCID 67776438N-(2-amino-4-(tert-butyl)phenyl)-2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetamide수율 82%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetic acid and 4-tert-butylbenzene-1,2-diamine (89.4 mg, 0.545 mmol) in N,N-dimethylformamide (4.5 mL) was treated with N,N-diisopropylethylamine (0.261 mL, 1.50 mmol) dropwise followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (259 mg, 0.681 mmol). The solution was allowed to stir at room temperature for 18 h during which time LCMS indicated the starting material had been consumed. The reaction mixture was concentrated under high vac. The residue was taken up in 30 mL ethyl acetate and 20 mL 1/1 H2O/sat NaHCO3 solution. The mixture was extracted and the aqueous phase was washed with 35 mL ethyl acetate. The combined organic phase was washed with two 20 mL portions of H2O, and 20 mL brine. The organic phase was dried over Na2SO4, filtered and concentrated to yield a tannish brown glass/stiff foam. The crude material was purified by flash chromatography (35 g silica gel; 4% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (272 mg, 82%) as a light tan glass/stiff foam which was a mixture of regioisomeric amides: MS (ESI+) for C41H53N7O6 m/z 728.8 (M+H)+; MS (ESI−) for C41H53N7O6 m/z 726.9 (M−H)−; HPLC purity >95%, (ret. time, 3.14, 3.17 min) two peaks observed due to amide regioisomers.

후처리

  1. customhad been consumed
  2. concentrationThe reaction mixture was concentrated under high vac
  3. extractionThe mixture was extracted
  4. washthe aqueous phase was washed with 35 mL ethyl acetate
  5. washThe combined organic phase was washed with two 20 mL portions of H2O, and 20 mL brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a tannish brown glass/stiff foam
  10. customThe crude material was purified by flash chromatography (35 g silica gel; 4% 7N NH3 in CH3OH/CH2Cl2)

출처 및 근거

ORD 기록
ord-6222990d16364ab1845890fdb8d8f87b
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580762B2

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