Trifluoroacetic acid → (3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

HRID 929250ノート

反応式

HRID 929250 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[N:22](COCC[Si](C)(C)C)[C:21]([O:31][C@H:32]3[C@H:36]4[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]4[O:34][CH2:33]3)=[N:20][C:5]2=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:31][C@H:32]3[C@H:36]4[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]4[O:34][CH2:33]3)=[N:20][C:5]2=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 131735112(3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

生成物 1

HCID 90067338(3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a r.t. solution of (3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (77 mg, 0.131 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (2 mL). The reaction was concentrated after 4 hours and diluted with ethyl acetate and saturated aqueous NaHCO3. This mixture was then extracted with ethyl acetate, and the combined the organic layers were washed with brine, dried over Na2SO4, and concentrated. This material was then purified via reverse phase HPLC on a 19×50 mm Waters Sunfire C18 column (5μ particle size) using a linear gradient with acetonitrile/water and buffering with 0.16% TFA at a flow rate 25 mL/min. The desired fractions were concentrated to obtain the title compound as a white sticky solid. LC-MS: calculated for C23H25ClN4O4 456.16 observed m/e: 457.33 (M+H)+ (Rt 1.08/2 min). 1H NMR δ (ppm) (DMSO): 7.76 (s, 1H), 7.30-7.28 (m, 4H), 7.19 (m, 1H), 5.38 (q, 1H), 4.80 (t, 1H), 4.33 (t, 1H), 4.14-4.09 (m, 2H), 3.85 (m, 1H), 3.74 (m, 1H), 3.59 (d, 2H), 3.40 (t, 1H), 2.85 (t, 2H), 2.68 (m, 1H), 1.85 (m, 4H).

後処理

  1. concentrationThe reaction was concentrated after 4 hours
  2. additiondiluted with ethyl acetate and saturated aqueous NaHCO3
  3. extractionThis mixture was then extracted with ethyl acetate
  4. washwere washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThis material was then purified via reverse phase HPLC on a 19×50 mm Waters Sunfire C18 column (5μ particle size)
  8. concentrationThe desired fractions were concentrated

出典と根拠

ORDレコード
ord-9713c8c7bda84abd803d5fb627f4dfe7
出典データセット
uspto-grants-2016_03
特許番号
US09290517B2

反応ノート

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