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

HRID 876002

反応式

HRID 876002 の反応式
[Si]([O:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:23]3[N:24]=[CH:25][C:26]4[C:31]5[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:30]=5[N:29]([CH:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[C:27]=4[N:28]=3)=[N:20][CH:21]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])([O-])=O.[K+].[K+].Cl>C1COCC1.CO.C(O)C.C(OCC)C>[CH:37]1([N:29]2[C:27]3[N:28]=[C:23]([NH:22][C:19]4[N:20]=[CH:21][C:16]([N:13]5[CH2:12][CH2:11][CH:10]([CH2:9][OH:8])[CH2:15][CH2:14]5)=[CH:17][CH:18]=4)[N:24]=[CH:25][C:26]=3[C:31]3[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:30]2=3)[CH2:38][CH2:39][CH2:40][CH2:41]1

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 58300053N-(5-(4-(((tert-Butyl(dimethyl)silyl)oxy)methyl)-1-piperidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

生成物 1

HCID 58299866(1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)-amino)-3-pyridinyl)-4-piperidinyl)methanol収率 27.5%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Compound 282 (118 mg, 205 μmol) was dissolved in dry THF (3 mL). Tetrabutylammonium fluoride, 1.0M in THF (0.75 mL, 750 μmol) was added and the reaction was stirred at room temperature for 80 minutes. The resulting solution was added to aqueous K2CO3 (10%, 30 mL) and extracted with dichloromethane+10% methanol (2×30 mL). The combined organics were dried (MgSO4) and evaporated 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 (1.5 mL) and HCl in ethanol (1.0M, 0.5 mL) was added. Diethyl ether (20 mL) was added to precipitate the product as a yellow solid, which was filtered and dried in vacuo to give compound 283 as a yellow solid (26 mg, 27%). 1H NMR (500 MHz, DMSO-d6) δ 9.87 (s, 1 H) 9.27-9.37 (m, 1 H) 8.11 (d, J=9.05 Hz, 1 H) 7.99-8.06 (m, 4 H) 7.48 (dd, J=9.17, 2.81 Hz, 1H) 5.46 (quin, J=9.11 Hz, 1 H) 4.50 (t, J=5.26 Hz, 2 H) 3.70 (d, J=11.98 Hz, 2 H) 2.61-2.71 (m, 2 H) 2.35 (d, J=12.72 Hz, 2 H) 2.10 (br. s., 2 H) 1.95-2.06 (m, 2 H) 1.77 (t, 4 H) 1.45-1.59 (m, 1 H) 1.28 (qd, J=12.23, 3.67 Hz, 2 H) ppm.

後処理

  1. extractionextracted with dichloromethane+10% methanol (2×30 mL)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customevaporated
  4. customto give an orange oil
  5. washSilica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol)
  6. customafforded a yellow solid
  7. customto precipitate the product as a yellow solid, which
  8. filtrationwas filtered
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-702cd6aac11546999d2f6faa557f1e80
出典データセット
uspto-grants-2015_03
特許番号
US08980903B2

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