Tetrahydrofuran → HCID 118061732、化合物

HRID 920794ノート

反応式

HRID 920794 の反応式
[F:1][C:2]1([F:16])[CH2:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)(C(O)=O)[CH2:3]1.C1C=CC(P([N:31]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[C:50]([C:51]([NH2:53])=[O:52])=[C:45]3[CH2:46][NH:47][CH2:48][CH2:49][N:44]3[N:43]=2)[CH:38]=[CH:39][C:40]=1[F:41].C1[CH2:58][O:57]CC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[C:50]([C:51]([NH2:53])=[O:52])=[C:45]3[CH2:46][N:47]([C:58]([NH:31][C:4]4([C:9]5[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=5)[CH2:3][C:2]([F:1])([F:16])[CH2:5]4)=[O:57])[CH2:48][CH2:49][N:44]3[N:43]=2)[CH:38]=[CH:39][C:40]=1[F:41]

参加物

7

反応物 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 1054874861773508-66-9HCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

生成物 1

HCID 118061732HCID 118061732、化合物収率 75%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

A stirred solution of Intermediate 308E (62.5 mg, 0.271 mmol) in toluene (2 mL) was added TEA (0.057 mL, 0.407 mmol), DPPA (0.062 mL, 0.271 mmol) and the reaction mixture was heated to 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (40 mg, 0.136 mmol) in THF (1 mL) and the reaction mixture was stirred at RT for 12 h. The reaction mass was diluted with ethyl acetate (5 mL), the organic layer was separated, washed with a 10% aq. NaHCO3 solution, water, brine, dried over Na2SO4, filtered and the filtrate concentrated under vacuum. The crude compound was purified by preparative HPLC to afford Compound 308 as a pale yellow solid (54 mg, 75%). The HPLC Retention times are 2.339 min. and 2.344 min. (Methods J and K respectively); MS(ES): −m/z=522 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.82-7.88 (m, 1H), 7.77-7.82 (m, 1H), 7.61-7.72 (m, 1H), 7.47 (s, 3H), 7.30-7.41 (m, 1H), 7.14 (s, 3H), 4.72 (s, 2H), 4.08-4.18 (m, 2H), 3.78-3.88 (m, 2H), 3.10-3.22 (m, 4H).

後処理

  1. temperatureThe reaction mass was cooled to RT and to it
  2. customthe organic layer was separated
  3. washwashed with a 10% aq. NaHCO3 solution, water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe crude compound was purified by preparative HPLC

出典と根拠

ORDレコード
ord-ed00550d7db3427b9bd276b65c619a6d
出典データセット
uspto-grants-2016_03
特許番号
US09273058B2

反応ノート

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