Cesium carbonate → 9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79150

反応式

HRID 79150 の反応式
Br[C:2]1[C:3]([F:21])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9]([NH:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.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]>[CH:16]1([N:15]2[C:9]3[N:10]=[C:11]([NH2:14])[N:12]=[CH:13][C:8]=3[C:7]3[CH:6]=[CH:5][N:4]=[C:3]([F:21])[C:2]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582998405-(3-Bromo-2-fluoro-4-pyridinyl)-N4-cyclopentyl-2,4-pyrimidinediamine

生成物 1

HCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine収率 85%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

Compound 244 (0.143 g, 0.41 mmol), and cesium carbonate (0.40 g, 1.2 mmol) were combined in 5 mL of anhydrous 1,4-dioxane. Nitrogen was bubbled through the solution briefly before adding Pd2(dba)3 (0.037 g, 0.041 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.047 g, 0.081 mmol). The solution was heated at 120° C. with microwave irradiation for 1 hour. The solution was purified on CombiFlash column (dry loaded) eluting with a gradient of 2% methanol/0.1% NH4OH (˜28% in water)/DCM to 7% methanol/0.35% NH4OH (˜28% in water)/DCM. The fractions containing the pure product were combined and concentrated under vacuum to give compound 245 (94 mg, 85%) as a light brownish solid. 1H NMR (500 MHz, DMSO-d6) δ 9.10 (1 H, s), 7.94 (1 H, dd, J=5.2, 1.5 Hz), 7.91 (1 H, dd, J=5.1, 2.9 Hz), 7.10 (2 H, br. s.), 5.38-5.49 (1 H, m), 2.10-2.23 (2 H, m), 1.93-2.08 (4 H, m), 1.64-1.79 (2 H, m) ppm; LCMS-ESI (POS), M/Z, M+1: Found 272.0.

後処理

  1. customNitrogen was bubbled through the solution briefly
  2. customThe solution was purified on CombiFlash column (dry loaded)
  3. washeluting with a gradient of 2% methanol/0.1% NH4OH (˜28% in water)/DCM to 7% methanol/0.35% NH4OH (˜28% in water)/DCM
  4. additionThe fractions containing the pure product
  5. concentrationconcentrated under vacuum

出典と根拠

ORDレコード
ord-274436a825854a9394d54ed1688b393c
出典データセット
uspto-grants-2014_09
特許番号
US08841312B2

関連ノート

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