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1-Propanol → (5r,7r)-4-(4-(1-(4-Chlorophenyl)-2-(isopropylamino)ethylamino)phenyl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol hydrochloride

HRID 521374
ノート
印刷プレビュー

反応式

HRID 521374 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:14][C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[CH2:9][NH:10][CH:11]([CH3:13])[CH3:12])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[N+](C1C=CC(C([O:45][C@H:46]2[C:50]3[N:51]=[CH:52][N:53]=[C:54](Cl)[C:49]=3[C@H:48]([CH3:56])[CH2:47]2)=O)=CC=1)([O-])=O.C(O)CC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([C:54]3[C:49]4[C@H:48]([CH3:56])[CH2:47][C@@H:46]([OH:45])[C:50]=4[N:51]=[CH:52][N:53]=3)=[CH:19][CH:20]=2)[CH2:9][NH:10][CH:11]([CH3:12])[CH3:13])=[CH:6][CH:7]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 674361641-(4-Chlorophenyl)-N2-isopropyl-N1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethane-1,2-diamineHCID 86651804(5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

生成物 1

HCID 67437652
(5r,7r)-4-(4-(1-(4-Chlorophenyl)-2-(isopropylamino)ethylamino)phenyl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol hydrochloride

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
90 °C

実験手順

1-(4-Chlorophenyl)-N2-isopropyl-N1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethane-1,2-diamine (0.075 g, 0.181 mmol), Pd(PPh3)4 (0.017 g, 0.015 mmol), and 2N Na2CO3 (0.226 mL, 0.452 mmol) were added to a solution of (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (0.050 g, 0.151 mmol) in n-propanol (0.464 mL, 0.151 mmol). The suspension was degassed by bubbling nitrogen through the solution. The dark suspension was heated at 90° C. for 14 hours. The mixture was cooled to room temperature and then concentrated. The resulting residue was diluted with ethyl acetate and filtered. The filtrate was washed with saturated NaHCO3 and brine. The organic layer was dried and concentrated. The resulting residue was purified by Biotage SP4 (C18, 25+ 0-100% ACN). The product-containing fractions were collected and repurified by Gilson C18 (5-95 ACN/H2O+1% TFA). Tubes containing product were identified by LCMS, collected and evaporated. The material was partially dissolved in CH2Cl2, and HCl (g) was bubbled through the mixture to precipitate solid (5R,7R)-4-(4-(1-(4-chlorophenyl)-2-(isopropylamino)ethylamino)phenyl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol hydrochloride (8.10 mg, 12%). LCMS APCI+(M+H+): 437 (100%), 439 (30%), rt 2.55 minutes. HPLC purity at 254 nm >99%, rt=2.17 minutes. 1H NMR (400 MHz, d6-acetone) δ 8.88 (s, 1H), 7.81 (d, J=8.2 Hz, 1H), 7.78 (d, J=8.6 Hz, 1H), 7.59 (d, J=3.5 Hz, 1H), 7.58 (d, J=3.1 Hz, 1H), 7.40 (d, J=8.2 Hz, 2H), 6.65 (t, J=9.0 Hz, 2H), 5.26 (m, 1H), 5.15 (td, J=7.4, 4.3 Hz, 1H), 3.88 (m, 2H), 3.62 (br s, 2H), 3.50 (br s, 1H), 2.17 (m, 2H), 1.45 (m, 2H), 1.41 (d, J=6.6 Hz, 6H), 1.10 (t, J=7.0 Hz, 3H), 0.88 (m, 1H).

後処理

  1. customThe suspension was degassed
  2. customby bubbling nitrogen through the solution
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationconcentrated
  5. additionThe resulting residue was diluted with ethyl acetate
  6. filtrationfiltered
  7. washThe filtrate was washed with saturated NaHCO3 and brine
  8. customThe organic layer was dried
  9. concentrationconcentrated
  10. customThe resulting residue was purified by Biotage SP4 (C18, 25+ 0-100% ACN)
  11. customThe product-containing fractions were collected
  12. customrepurified by Gilson
  13. additionTubes containing product
  14. customcollected
  15. customevaporated
  16. dissolutionThe material was partially dissolved in CH2Cl2
  17. customHCl (g) was bubbled through the mixture
  18. customto precipitate solid (5R,7R)-4-(4-(1-(4-chlorophenyl)-2-(isopropylamino)ethylamino)phenyl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol hydrochloride (8.10 mg, 12%)
  19. custom437 (100%), 439 (30%), rt 2.55 minutes
  20. customat 254 nm >99%, rt=2.17 minutes

出典と根拠

ORDレコード
ord-179f353998104122a6a6db02ded7c2e6
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09328091B2

反応ノート

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