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 334872노트

반응식

HRID 334872 반응식
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

참가 물질

7

반응물 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 hydrochloride2회HCID 69965156(R)-2'-Oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid2회

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
23 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5778f1460fd9466a99b85dbf45e6abf5
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883807B2

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