Phenylboronic Acid → (7R,8R,9R)-10-acetyl-3,9-diphenyl-7-(2-methoxyethoxy)-2-methyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 985108노트

반응식

HRID 985108 반응식
[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16](Br)[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C@H:5]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:3])[CH3:2].[C:37]1(B(O)O)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[F-].[K+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C@H:5]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:3])[CH3:2]

참가 물질

7

반응물 4

HCID 66827Phenylboronic AcidHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 69586421HCID 69586421, 화합물

생성물 1

HCID 69586312(7R,8R,9R)-10-acetyl-3,9-diphenyl-7-(2-methoxyethoxy)-2-methyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
25 °C

실험 절차

2.61 g (4.67 mmol) (7R,8R,9R)-10-acetyl-3-bromo-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine, 0.63 g (5.14 mmol) phenylboronic acid, 0.89 g (15.4 mmol) KF (spray-dried), 0.14 g (0.15 mmol) Pd2(dba)3, 0.07 g (0.36 mmol/10 wt % solution in hexane)P(t-Bu)3 and THF (30 ml) are added to a Schlenk tube under argon. Afterwards the Schlenk tube is evacuated and refilled with argon in a freeze-pump-thaw cycles technique three times. The reaction mixture is stirred under argon for 2 d at 25° C. Subsequently the reaction is diluted by adding of ethyl acetate and then filtrated through silica gel. The concentrated crude product is purified by column chromatography (diethyl ether/petrol ether: 6/4) to give 1.80 g (3.24 mmol/70%) of the title compound as an amorphous colourless solid. 1H-NMR (200 MHz,[D6] DMSO): δ=1.20 (s, 9H), 2.20 (s, 3H), 2.43 (s, 3H), 3.30 (s, 3H), 3.40-3.57 (m, 2H), 3.88 (t, 2H), 4.64 (d, 1H), 5.35 (t, 1H), 5.83 (d, 1H), 7.00 (d, 1H), 7.10-7.30 (m, 5H), 7.41-7.68 (m, 5H), 8.24 (d, 1H).

후처리

  1. customAfterwards the Schlenk tube is evacuated
  2. additionrefilled with argon in a freeze-pump-thaw cycles technique three times
  3. additionSubsequently the reaction is diluted
  4. additionby adding of ethyl acetate
  5. filtrationfiltrated through silica gel
  6. concentrationThe concentrated crude product
  7. customis purified by column chromatography (diethyl ether/petrol ether: 6/4)

출처 및 근거

ORD 기록
ord-9767a9241af5472181cc6ef76d26e8a4
출처 데이터셋
uspto-grants-2005_03
특허 번호
US06869949B2

반응 노트

불러오는 중…