Hydrochloric Acid → (3R)-1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-3-pyrrolidinol

HRID 875998ノート

反応式

HRID 875998 の反応式
[Si]([O:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:29]5[CH:30]=[CH:31][N:32]=[C:33]([F:34])[C:28]=5[N:27]([CH:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)[C:25]=4[N:26]=3)=[N:18][CH:19]=2)[CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl.C(OCC)C>C1COCC1.CO.C(O)C>[CH:35]1([N:27]2[C:25]3[N:26]=[C:21]([NH:20][C:17]4[N:18]=[CH:19][C:14]([N:11]5[CH2:12][CH2:13][C@@H:9]([OH:8])[CH2:10]5)=[CH:15][CH:16]=4)[N:22]=[CH:23][C:24]=3[C:29]3[CH:30]=[CH:31][N:32]=[C:33]([F:34])[C:28]2=3)[CH2:36][CH2:37][CH2:38][CH2:39]1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 2724141Tetrabutylammonium FluorideHCID 58299699N-(5-((3R)-3-((tert-butyl(dimethyl)silyl)oxy)-1-pyrrolidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

生成物 1

HCID 58299703(3R)-1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-3-pyrrolidinol収率 50%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Compound 278 (58 mg, 106 mmol) was dissolved in THF (2 mL). Tetrabutylammonium fluoride, 1.0M in THF (0.5 mL, 0.500 mmol) was added and the reaction stirred at room temperature for 4 hours. The solvent was removed to give an orange oil. Silica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol) afforded a yellow solid. This residue was taken up in methanol (2 mL) and HCl in ethanol (1.0M, 0.5 mL) was added. Diethyl ether (20 mL) was added to precipitate the product, which was filtered and dried in vacuo to give compound 277 as a yellow solid (23 mg, 50%). 1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1 H) 9.25-9.35 (m, 1 H) 7.94-8.11 (m, 4 H) 7.62-7.77 (m, 2 H) 7.05 (dd, J=8.93, 2.81 Hz, 1 H) 5.37-5.54 (m, 1 H) 4.99 (d, J=3.91 Hz, 1 H) 4.44 (br. s., 1 H) 3.46 (dd, J=10.03, 4.89 Hz, 2 H) 3.05-3.16 (m, 1 H) 2.26-2.42 (m, 3 H) 1.96-2.20 (m, 8 H) 1.85-1.96 (m, 2 H) 1.66-1.83 (m, 3 H) ppm.

後処理

  1. customThe solvent was removed
  2. customto give an orange oil
  3. washSilica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol)
  4. customafforded a yellow solid
  5. customto precipitate the product, which
  6. filtrationwas filtered
  7. customdried in vacuo

出典と根拠

ORDレコード
ord-8865f967e8724d51b7b88107242b08df
出典データセット
uspto-grants-2015_03
特許番号
US08980903B2

反応ノート

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