Triethylamine → 5-(3-{(3R,4R)-1-tert-butoxycarbonyl-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidin-4-yl}-ureido)-indazole-1-carboxylic acid t-butyl ester

HRID 497461ノート

反応式

HRID 497461 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[C@H:10]([C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:18]2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:38]([O:42][C:43]([N:45]1[C:53]2[C:48](=[CH:49][C:50]([NH:54][C:55](OC3C=CC=CC=3)=[O:56])=[CH:51][CH:52]=2)[CH:47]=[N:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>C(#N)C.C(OCC)(=O)C>[C:38]([O:42][C:43]([N:45]1[C:53]2[C:48](=[CH:49][C:50]([NH:54][C:55]([NH:14][C@@H:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][C@H:10]3[C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[CH2:18]3)=[O:16])=[O:56])=[CH:51][CH:52]=2)[CH:47]=[N:46]1)=[O:44])([CH3:41])([CH3:39])[CH3:40]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 69747061HCID 69747061、化合物HCID 69748878(3R,4R)-4-amino-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester

生成物 1

HCID 697487235-(3-{(3R,4R)-1-tert-butoxycarbonyl-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidin-4-yl}-ureido)-indazole-1-carboxylic acid t-butyl ester収率 61.2%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

In a dry flask (3R,4R)-4-Amino-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester (72 mg, 0.171 mmol) was dissolved in acetonitrile (2 mL) and triethylamine (25 μL, 0.179 mmol) and 5-(phenoxycarbonylamino)-1-indazolecarboxylic acid 1-tert-butyl ester (72 mg, 0.204 mmol) were added. The reaction mixture was stirred for 64 hours while heating to 60° C. The reaction mixture was cooled, diluted with ethyl acetate, washed twice with water and once with brine. The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (71 mg, 61%). 1H NMR (300 MHz, CDCl3), δ: 8.09 (m, 2H), 7.90 (2s, 1H), 7.44 (m, 1H), 7.10 (m, 1H), 6.99 (m, 1H), 6.83 (m, 2H), 4.90 (bs, 1H), 4.43 (bd, 1H, J=11), 4.22 (bs, 2H), 3.98 (bm, 2H), 3.14 (t, 1H, J=13), 2.75 (bm, 4H), 2.45 (bm, 3H), 1.94 (bm, 3H), 1.73 (2s, 9H), 1.48 (m, 9H), 1.45 (bm, 3H), 1.22 (bm, 1H). HRMS (ESI), C36H48FN6O6 m+/z: calc.=679.3619, found=679.3621.

後処理

  1. temperatureThe reaction mixture was cooled
  2. washwashed twice with water and once with brine
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-3d2925c7232742309d160a0482634c56
出典データセット
uspto-grants-2005_09
特許番号
US06949546B2

反応ノート

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