Ammonia → 2-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6,8-dimethoxy-isoquinolin-4-ylamino]-thiazole-4-carboxylic acid

HRID 14694

Reaktionsgleichung

Reaktionsgleichung von HRID 14694
[C:1](Cl)(Cl)=[S:2].[NH2:5][C:6]1[C:15]2[C:10](=[C:11]([O:18][CH3:19])[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[N:8][CH:7]=1.C[CH2:33][N:34](C(C)C)C(C)C.N.BrC[C:44](=O)[C:45]([OH:47])=[O:46]>C1COCC1>[O:31]=[C:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:29](=[O:30])[N:21]1[CH2:20][C:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])[C:6]([NH:5][C:33]2[S:2][CH:1]=[C:44]([C:45]([OH:47])=[O:46])[N:34]=2)=[CH:7][N:8]=1

Komponenten

7

Edukt 5

HCID 222AmmoniaHCID 10040ThiophosgeneHCID 70684Bromopyruvic AcidHCID 81531DiisopropylethylamineHCID 593410902-(4-Amino-6,8-dimethoxy-isoquinolin-1-ylmethyl)-isoindole-1,3-dione

Produkt 1

HCID 593410932-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6,8-dimethoxy-isoquinolin-4-ylamino]-thiazole-4-carboxylic acidAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Thiophosgene (146 μL, 1.92 mmol) was added to a solution of Example 45C (580 mg, 1.6 mmol) and DIEA (670 μL) in THF (10 mL). After stirring for 1 h, the reaction was poured over aqueous ammonia and extracted with EtOAc. Organics were dried (MgSO4) and concentrated. The resulting crude thiourea was dissolved in THF (5 mL). Bromopyruvic acid (320 mg, 1.92 mmol) was added, and the reaction stirred for 2 h. Purification by silica gel chromatography (10% MeOH/CHCl3) gave 590 mg (75%) of the title compound as a tan solid. H1-NMR (MeOD-d4): δ 9.95 (br s, 1H), 8.81 (br s, 1H), 7.87-7.96 (m, 4H), 7.60 (br s, 1H), 7.14 (s, 1H), 6.86 (s, 1H), 5.41 (s, 2H), 4.09 (s, 3H), 3.94 (s, 3H). MS (ES) (M+H) calc'd for C24H18N4O6S, 491; found 491.

Aufarbeitung

  1. extractionextracted with EtOAc
  2. dry with materialOrganics were dried (MgSO4)
  3. concentrationconcentrated
  4. dissolutionThe resulting crude thiourea was dissolved in THF (5 mL)
  5. stirringthe reaction stirred for 2 h
  6. customPurification by silica gel chromatography (10% MeOH/CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-aac9a72a39a84e959ebd805c61d91840
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732446B1

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