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Sodium Bicarbonate → 1,1-dimethylethyl 4-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate

HRID 1909985
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HRID 1909985 반응식
[NH2:1][C:2]1[C:3]2[C:10](Br)=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:25][C:26]1[CH:27]=[C:28]([CH2:32][C:33]([N:35]2[C:43]3[C:38](=[CH:39][C:40](B4OC(C)(C)C(C)(C)O4)=[CH:41][CH:42]=3)[CH2:37][CH2:36]2)=[O:34])[CH:29]=[CH:30][CH:31]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.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>[NH2:1][C:2]1[C:3]2[C:10]([C:40]3[CH:39]=[C:38]4[C:43](=[CH:42][CH:41]=3)[N:35]([C:33](=[O:34])[CH2:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([CH3:25])[CH:27]=3)[CH2:36][CH2:37]4)=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1
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참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 668237951,1-dimethylethyl 4-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylateHCID 668241231-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole

생성물 1

HCID 668238551,1-dimethylethyl 4-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate수율 80.4%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To 1,1-dimethylethyl 4-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate (200 mg, 0.505 mmol), and 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (228 mg, 0.606 mmol) dissolved in 1,4-Dioxane (4 mL) was added saturated aqueous NaHCO3 (2 mL). The mixture was then bubbled with N2 gas for 10 minutes and then Pd(Ph3P)4 (58.3 mg, 0.050 mmol) was added and then bubbled for 5 additional minutes. Then reaction was then capped and heated at 100° C. overnight. The mixture was allowed to cool then diluted with water (10 mL) then extracted with EtOAc (3×20 ml). The organics were combined, washed with brine, dried over MgSo4, filtered and concentrated to isolate a amber color oil. The oil was then purified on a 25 g Biotage SNAP column conditioned with Hexane and eluting with a gradient of 0 to 10% MeOH in DCM for 30 minutes to afford 1,1-dimethylethyl 4-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate (230 mg, 80% yield) as a amber color oil. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.13 (s, 1H), 7.45 (s, 1H), 7.32 (s, 1H), 7.20-7.26 (m, 2H), 7.12 (s, 1H), 7.09 (t, J=7.58 Hz, 2H), 4.71-4.83 (m, 1H), 4.20 (t, J=8.46 Hz, 2H), 4.08-4.15 (m, 2H), 3.94 (s, 2H), 3.82 (s, 2H), 3.20 (t, J=8.46 Hz, 2H), 2.95 (br. s., 2H), 2.31 (s, 3H), 1.86-1.97 (m, 4H), 1.43 (s, 9H).

후처리

  1. customThe mixture was then bubbled with N2 gas for 10 minutes
  2. custombubbled for 5 additional minutes
  3. customThen reaction
  4. customwas then capped
  5. temperatureto cool
  6. extractionthen extracted with EtOAc (3×20 ml)
  7. washwashed with brine
  8. customdried over MgSo4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto isolate a amber color oil
  12. customThe oil was then purified on a 25 g Biotage SNAP column
  13. washeluting with a gradient of 0 to 10% MeOH in DCM for 30 minutes

출처 및 근거

ORD 기록
ord-d11c3e23b96d4849b839bea1b78d04ce
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08598156B2

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