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

HRID 14694

反応式

HRID 14694 の反応式
[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

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-aac9a72a39a84e959ebd805c61d91840
出典データセット
uspto-grants-2010_06
特許番号
US07732446B1

関連ノート

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