Diisopropylethylamine → (2R)-N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 334872ノート

反応式

HRID 334872 の反応式
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[O:28]=[C:29]1[NH:37][C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C@:30]21[CH2:45][C:44]1[C:39](=[CH:40][CH:41]=[C:42]([C:46]([OH:48])=O)[CH:43]=1)[CH2:38]2.Cl.[NH2:50][C@H:51]1[CH2:56][C@@H:55]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C@@H:54]([CH3:63])[N:53]([CH2:64][C:65]([F:68])([F:67])[F:66])[C:52]1=[O:69].C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[CH3:63][C@H:54]1[N:53]([CH2:64][C:65]([F:68])([F:66])[F:67])[C:52](=[O:69])[C@@H:51]([NH:50][C:46]([C:42]2[CH:43]=[C:44]3[C:39](=[CH:40][CH:41]=2)[CH2:38][C@:30]2([C:31]4[C:32](=[N:33][CH:34]=[CH:35][CH:36]=4)[NH:37][C:29]2=[O:28])[CH2:45]3)=[O:48])[CH2:56][C@H:55]1[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68749751(3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride2 回HCID 69965156(R)-2'-Oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid2 回

生成物 1

HCID 69965196(2R)-N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
23 °C

実験手順

Benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (679 mg, 1.53 mmol) was added to a solution of (2R)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (described in Intermediate 1) (364 mg, 1.30 mmol), (3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride (described in Intermediate 4) (380 mg, 1.18 mmol), and N,N-diisopropylethylamine (2.06 mL, 11.8 mmol) in DMF (6 mL), and the resulting mixture was stirred at 23° C. for 16 h. The reaction mixture was then diluted with water (200 mL), and the precipitate was collected by filtration, washed with water, and air dried. The crude product was purified by flash column chromatography on silica gel, eluting with hexanes initially, grading to 100% EtOAc to afford the title compound. HRMS: m/z=549.2123, calculated m/z=549.2108 for C30H28F3N4O3. 1H NMR (500 MHz, CDCl3) δ 8.74 (s, 1H), 8.14 (dd, 1H, J=5.3, 1.5 Hz), 7.76 (s, 1H), 7.73 (d, 1H, J=7.8 Hz), 7.37-7.33 (m, 3H), 7.28 (t, 1H, J=7.6 Hz), 7.22-7.19 (m, 3H), 7.00 (d, 1H, J=7.4 Hz), 6.82 (dd, 1H, J=7.4, 5.3 Hz), 4.99-4.89 (1H, m), 4.53 (dt, 1H, J=11.6, 5.9 Hz), 3.93 (p, 1H, J=6.0 Hz), 3.69 (dd, 2H, J=16.1, 9.5 Hz), 3.64 (m, 1H), 3.34-3.24 (m, 1H), 3.11 (dd, 2H, J=16.0, 6.5 Hz), 2.81 (m, 1H), 2.56 (q, 1H, J=12.5 Hz), 1.06 (d, 3H, J=6.5 Hz).

後処理

  1. filtrationthe precipitate was collected by filtration
  2. washwashed with water, and air
  3. customdried
  4. customThe crude product was purified by flash column chromatography on silica gel
  5. washeluting with hexanes initially

出典と根拠

ORDレコード
ord-5778f1460fd9466a99b85dbf45e6abf5
出典データセット
uspto-grants-2014_11
特許番号
US08883807B2

反応ノート

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