Carbonochloridic acid, 5-methyl-2-(1-methylethyl)cyclohexyl ester, (1S,2R,5S)- → (R)-1-((2-(1-(Benzo[d][1,3]dioxol-6-yl)cyclopropanecarboxamido)thiazol-5-yl)(2-chlorophenyl)methyl)pyrrolidin-3-yl (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl carbonate

HRID 1673118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1673118
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:21]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[Cl:34])[N:22]5[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]5)=[CH:19][N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.Cl[C:36]([O:38][C@H:39]1[CH2:44][C@@H:43]([CH3:45])[CH2:42][CH2:41][C@@H:40]1[CH:46]([CH3:48])[CH3:47])=[O:37]>ClCCl.CN(C)C1C=CN=CC=1.CO>[C:36](=[O:37])([O:38][C@H:39]1[CH2:44][C@@H:43]([CH3:45])[CH2:42][CH2:41][C@@H:40]1[CH:46]([CH3:48])[CH3:47])[O:27][C@@H:24]1[CH2:25][CH2:26][N:22]([CH:21]([C:18]2[S:17][C:16]([NH:15][C:13]([C:10]3([C:8]4[CH:7]=[CH:6][C:5]5[O:1][CH2:2][O:3][C:4]=5[CH:9]=4)[CH2:12][CH2:11]3)=[O:14])=[N:20][CH:19]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[Cl:34])[CH2:23]1

Komponenten

6

Edukt 2

HCID 2733329Carbonochloridic acid, 5-methyl-2-(1-methylethyl)cyclohexyl ester, (1S,2R,5S)-HCID 58609841HCID 58609841, Verbindung

Produkt 1

HCID 58048496(R)-1-((2-(1-(Benzo[d][1,3]dioxol-6-yl)cyclopropanecarboxamido)thiazol-5-yl)(2-chlorophenyl)methyl)pyrrolidin-3-yl (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl carbonateAusbeute 49,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((R)-3-hydroxypyrrolidin-1-yl)methyl)thiazol-2-yl)cyclopropanecarboxamide (3.00 g, 6.02 mmol) was suspended in 200 mL of anhydrous dichloromethane containing N,N-dimethylpyridin-4-amine (2.20 g, 18.0 mmol). (1S,2R,5S)-2-Isopropyl-5-methylcyclohexyl chloroformate (1.91 mL, 9.00 mmol) was slowly added to the suspension and the resulting mixture was heated to reflux for 16 hours. The resulting pale yellow solution was allowed to cool to room temperature, diluted with 20 mL of methanol, and then evaporated to dryness. The crude reaction mixture was separated on 330 g of silica gel utilizing a gradient of 0-5% methanol in dichloromethane to yield the pure product as a pale yellow solid (2.0087 g, 2.9529 mmol, 49.1%). ESI-MS m/z calc. 679.3. found; 680.5 (M+1)+; Retention time 3.88 minutes.

Aufarbeitung

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 16 hours
  3. customevaporated to dryness
  4. customThe crude reaction mixture
  5. customwas separated on 330 g of silica gel utilizing a gradient of 0-5% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-3277fd1ad17a411b8b04a75c4e0fd100
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07999113B2

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