Triethylamine → (6S)-N-[(3S,5S,6R)-6-Methyl-5-(2-methylphenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide

HRID 406572ノート

反応式

HRID 406572 の反応式
Cl.C(N=C=NCCCN(C)C)C.[O:13]=[C:14]1[NH:22][C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:16]2[C@@:15]21[CH2:33][C:25]1=[N:26][CH:27]=[C:28]([C:30](O)=[O:31])[CH:29]=[C:24]1[CH2:23]2.Cl.[NH2:35][C@H:36]1[CH2:41][C@@H:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[CH3:48])[C@@H:39]([CH3:49])[N:38]([CH2:50][C:51]([F:54])([F:53])[F:52])[C:37]1=[O:55].N1C2C(=NC=CC=2)N(O)N=1.C(N(CC)CC)C>CN(C=O)C>[CH3:49][C@H:39]1[N:38]([CH2:50][C:51]([F:53])([F:54])[F:52])[C:37](=[O:55])[C@@H:36]([NH:35][C:30]([C:28]2[CH:29]=[C:24]3[CH2:23][C@@:15]4([C:16]5[C:17](=[N:18][CH:19]=[CH:20][CH:21]=5)[NH:22][C:14]4=[O:13])[CH2:33][C:25]3=[N:26][CH:27]=2)=[O:31])[CH2:41][C@H:40]1[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[CH3:48]

参加物

7

反応物 5

HCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68746980(S)-2'-oxo-1',2',5,7-tetrahydrospiro(cyclopenta(b)pyridine-6,3'-pyrrolo(2,3-b)-bipyridine)-3-carboxylic acid2 回HCID 68754170(3S,5S,6R)-3-amino-6-methyl-5-(2-methylphenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride2 回

生成物 1

HCID 68751311(6S)-N-[(3S,5S,6R)-6-Methyl-5-(2-methylphenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
23 °C

実験手順

N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.10 g, 0.53 mmol) was added to a solution of (6S)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylic acid (described in Intermediate 1) (111 mg, 0.39 mmol), (3S,5S,6R)-3-amino-6-methyl-5-(2-methylphenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride (described in Intermediate 6) (127 mg, 0.38 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol(HOAt, 15 mg, 0.11 mmol), and triethylamine (0.16 mL, 0.91 mmol) in DMF (3 mL), and the resulting mixture was stirred at 23° C. for 18 h. The reaction mixture was then partitioned between saturated aqueous sodium bicarbonate solution (10 mL) and ethyl acetate (2×30 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with 1% methanol→7% methanol/dichloromethane to afford the title compound. HRMS: m/z=564.2219 (M+1), calculated m/z=564.2234 for C30H28F3N5O3. 1H NMR (500 MHz, CDCl3) δ 8.91 (s, 1H), 8.56 (s, 1H), 8.17 (dd, 1H, J=5.0, 1.5 Hz), 8.05 (s, 1H), 7.30 (d, 1H, J=5.0 Hz), 7.20 (m, 3H), 7.12 (m, 2H), 6.89 (dd, 1H, J=7.5, 5.0 Hz), 5.00-4.94 (m, 1H), 4.55 (m, 1H), 3.93-3.90 (m, 1H), 3.81-3.76 (m, 2H), 3.68 (d, 1H, J=16.5 Hz), 3.31-3.23 (m, 2H), 3.17 (d, 1H, J=16.5 Hz), 2.75-2.67 (m, 2H), 2.41 (s, 3H), 1.11 (d, 3H, J=6.5 Hz).

後処理

  1. customThe reaction mixture was then partitioned between saturated aqueous sodium bicarbonate solution (10 mL) and ethyl acetate (2×30 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with 1% methanol

出典と根拠

ORDレコード
ord-6e1c1403797e4b3086155c0b100f2d13
出典データセット
uspto-grants-2014_06
特許番号
US08754096B2

反応ノート

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