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 2378999Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2378999
[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 a white 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-b2e43c5c7c754892a86fcea321fc9232
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470680B2

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