Triethylamine → (S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one

HRID 132505Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 132505
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](O)=[O:18])[CH2:15][C:4]=2[CH:3]=1.[NH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[NH:28][C:27]1=[O:41].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:24])([F:23])[F:25])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:18])[N:38]3[CH2:37][CH2:36][C:29]4([C:30]5[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=5)[NH:26][C:27](=[O:41])[NH:28]4)[CH2:40][CH2:39]3)[CH2:15][C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 497603501'H-Spiro[piperidine-4,4'-quinazolin]-2'(3'H)-oneHCID 59732027(S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid

Produkt 1

HCID 11978423(S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-oneAusbeute 79,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (50 mg, 0.133 mmol) in dichloromethane (25 mL) was added 1′H-spiro[piperidine-4,4′-quinazolin]-2′(3′H)-one (31 mg, 0.14 mmol) followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (47 mg, 0.15 mmol) and triethylamine (1.0 mL). After 12 h, the reaction mixture was washed with aqueous NaHCO3 followed by 1.0 M HCl and dried (Na2SO4). The solvent was removed and the crude product was purified by flash chromatography using 7% MeOH in dichloromethane to give (S)-4-chloro-7-(2-oxo-2-(2′-oxo-2′,3′-dihydro-1′H-spiro[piperidine-4,4′-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (61 mg, 79%) as awhite powder. MS (ESI) 575 (M+H); Rf=2.133.

Aufarbeitung

  1. washthe reaction mixture was washed with aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. customThe solvent was removed
  4. customthe crude product was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-69458b9150c34983897d5516e2277aa9
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384931B2

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