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HOAt → N-(2-amino-4-(tert-butyl)phenyl)-3-(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)(isopropyl)amino)cyclobutyl)propanamide

HRID 2040732
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HRID 2040732 반응식
[CH3:1][O:2][C:3]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][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]([CH:37]([CH3:39])[CH3:38])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34](O)=[O:35])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=NC2N(O)N=NC=2C=1.[C:80]([C:84]1[CH:85]=[C:86]([NH2:91])[C:87]([NH2:90])=[CH:88][CH:89]=1)([CH3:83])([CH3:82])[CH3:81]>C(Cl)Cl>[NH2:91][C:86]1[CH:85]=[C:84]([C:80]([CH3:83])([CH3:81])[CH3:82])[CH:89]=[CH:88][C:87]=1[NH:90][C:34](=[O:35])[CH2:33][CH2:32][CH:30]1[CH2:31][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:24])([CH3:25])[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:40]=[CH:41][C:42]([O:44][CH3:45])=[CH:43][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[O:17]2)[CH:37]([CH3:38])[CH3:39])[CH2:29]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 181649HOAtHCID 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 677769633-(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)(isopropyl)amino)cyclobutyl)propanoic acid

생성물 1

HCID 67775308
N-(2-amino-4-(tert-butyl)phenyl)-3-(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)(isopropyl)amino)cyclobutyl)propanamide
수율 50.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

To a solution of 3-(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)(isopropyl)amino)cyclobutyl)propanoic acid (1.1 g, 1.76 mmol), HATU (1 g, 2.64 mmol), HOAT (359 mg, 2.64 mmol) in DCM (30 mL) was added a solution of 4-tert-butylbenzene-1,2-diamine (433 mg, 2.64 mmol) and TEA (533 mg, 5.28 mmol) in DCM (10 mL) dropwise, then the resultant reaction mixture was stirred at rt overnight. After diluted with DCM (50 mL), the mixture was washed water (30 mL×3), dried and concentrated. The crude was purified by SGC (DCM:MeOH=100:1 to 40:1) to afford the desired compound (680 mg, yield: 50%) as a white solid. 1H NMR (500 MHz, MeOD): δH 8.16 (s, 1H), 7.19 (d, J=3.5 Hz, 1H), 7.14-7.10 (m, 1.7H),6.99-6.97 (m, 0.6H), 6.92 (s, 0.6H), 6.77 (dd, J=8.0, 2.0 Hz, 1H), 6.66-6.65 (m, 1H), 6.54-6.53 (m, 1H), 6.42 (d, J=8.0 Hz, 1H), 6.20 (d, J=2.0 Hz, 1H), 5.36-5.35 (m, 1H), 4.96-4.95 (m, 1H), 4.65 (s, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 3.17-2.73 (m, 4H), 2.33-1.71 (m, 8H), 1.58 (s, 3H), 1.53-1.50 (m, 1H), 1.38 (s, 3H), 1.28 (s, 9H), 1.0 (d, J=5.5 Hz, 3H), 0.84 (d, J=5.0 Hz, 3H) ppm; LC-MS (m/z): 770.0 [M+1]+.

후처리

  1. customthe resultant reaction mixture
  2. washthe mixture was washed water (30 mL×3)
  3. customdried
  4. concentrationconcentrated
  5. customThe crude was purified by SGC (DCM:MeOH=100:1 to 40:1)

출처 및 근거

ORD 기록
ord-933058f7fb5e446e8e49460dd8c4650f
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08580762B2

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