Diisopropylethylamine → 1-(3-(4-(Pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione

HRID 512124노트

반응식

HRID 512124 반응식
[C:1]([C:4]1[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=1)[CH2:7][N:8]1[C:17]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=2[C:11](=[O:18])[NH:10][C:9]1=[O:19])(O)=[O:2].[N:23]1[CH:28]=[CH:27][CH:26]=[N:25][C:24]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[N:23]1[CH:28]=[CH:27][CH:26]=[N:25][C:24]=1[N:29]1[CH2:34][CH2:33][N:32]([C:1]([C:4]2[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=2)[CH2:7][N:8]2[C:17]3[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[C:11](=[O:18])[NH:10][C:9]2=[O:19])=[O:2])[CH2:31][CH2:30]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 887471-(2-Pyrimidinyl)piperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89545385HCID 89545385, 화합물

생성물 1

HCID 715521911-(3-(4-(Pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione수율 23.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 1-(3-carboxybenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (0.2 mmol), 1-(pyrimidin-2-yl)piperazine (0.2 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.26 mmol) and N,N-diisopropylethylamine (DIPEA, 0.4 mmol) in DMF (5 mL) was stirred at room temperature overnight. To the mixture was added 50 mL of water and it was extracted with EA (50 mL×3). The organic layer was washed by 1 N hydrochloric acid (50 mL×1) and saturated NaCl aquenous solution (50 mL×1), dried with anhydrous sodium sulfate, and concentrated to give the crude product, which was purified by flash chromatography (DCM: MeOH=20:1) to give the title compound (20.43 mg, 23.3% yield) as white solid. 1H NMR (DMSO-d6): 11.35 (s, 1H), 8.39 (d, J=4.5 Hz, 2H), 7.48-7.41 (m, 1H), 7.36-7.24 (m, 3H), 6.67 (t, J=4.8 Hz, 1H), 5.10 (s, 2H), 3.88-3.20 (m, 8H), 2.46-2.42 (m, 2H), 2.25-2.21 (m, 2H), 1.69-1.43 (m, 4H). MS: m/z 447.4 [M+H]+.

후처리

  1. extractionwas extracted with EA (50 mL×3)
  2. washThe organic layer was washed by 1 N hydrochloric acid (50 mL×1) and saturated NaCl aquenous solution (50 mL×1)
  3. dry with materialdried with anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by flash chromatography (DCM: MeOH=20:1)

출처 및 근거

ORD 기록
ord-02e31e72d2974c709a0609fdb05f4e43
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102631B2

반응 노트

불러오는 중…