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Potassium Phosphate, Tribasic → 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-chloro-2,3-dihydro-1H-indole-1-carboxylate

HRID 1910098
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HRID 1910098 반응식
Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH3:12])[CH:3]=1.[Cl:13][C:14]1[C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][CH2:17][N:18]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[NH2:11][C:9]1[C:10]2[C:2]([C:22]3[C:14]([Cl:13])=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:17][CH2:16]4)=[CH:3][N:4]([CH3:12])[C:5]=2[N:6]=[CH:7][N:8]=1
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참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 665609385-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 66823555tert-Butyl 4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxylate

생성물 1

HCID 668239601,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-chloro-2,3-dihydro-1H-indole-1-carboxylate수율 79.7%

시약·촉매·용매 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 962Water용매2회
HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (510 mg, 2.246 mmol), 1,1-dimethylethyl 4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (853 mg, 2.246 mmol), Pd2(dba)3 (103 mg, 0.112 mmol) and Potassium Phosphate (K3PO4) (954 mg, 4.49 mmol) and (t-Bu)3PHBF4 (6.52 mg, 0.022 mmol) in 1,4-Dioxane (10 mL) and Water (3.3 mL) in a sealed tube was heated at 100° C. on a stirrer hot plate. At this time, LCMS analysis indicated good conversion, so the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×100 mL), and the combined organics dried over sodium sulfate and concentrated. The residue was dissolved in DCM (ca. 100 mL), concentrated to minimum volume (ca. 40 mL), then purified by flash chromatography (0-100% EtOAc in hexanes, 40-g silica gel column) to afford 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-chloro-2,3-dihydro-1H-indole-1-carboxylate (0.716 g) as a yellow solid. LC-MS (ES) m/z=400 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52 (s, 9H), 3.14 (t, J=8.59 Hz, 2H), 3.74 (s, 3H), 3.96-4.07 (m, 2H), 5.73-6.04 (m, 2H), 7.15-7.26 (m, 2H), 7.57-7.80 (m, 1H), 8.13 (s, 1H).

후처리

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. dry with materialthe combined organics dried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in DCM (ca. 100 mL)
  5. concentrationconcentrated to minimum volume (ca. 40 mL)
  6. custompurified by flash chromatography (0-100% EtOAc in hexanes, 40-g silica gel column)

출처 및 근거

ORD 기록
ord-50a78bdd85bb4d628f5d43ebe1b03a07
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08598156B2

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