Hydrochloric Acid → (2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid

HRID 1289241ノート

反応式

HRID 1289241 の反応式
[NH2:1][C@@H:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4].[F:16][C:17]1[CH:36]=[C:35]([N:37]([CH3:61])[CH:38]2[C:42]3[CH:43]=[C:44]4[C:49](=[CH:50][C:41]=3[CH2:40][CH2:39]2)[N:48]=[C:47]([CH3:51])[N:46]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[C:45]4=[O:60])[CH:34]=[CH:33][C:18]=1[C:19](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:20].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl>CN(C=O)C.CO.O>[F:16][C:17]1[CH:36]=[C:35]([N:37]([CH3:61])[CH:38]2[C:42]3[CH:43]=[C:44]4[C:49](=[CH:50][C:41]=3[CH2:40][CH2:39]2)[N:48]=[C:47]([CH3:51])[N:46]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:56])([CH3:57])[CH3:58])[C:45]4=[O:60])[CH:34]=[CH:33][C:18]=1[C:19]([NH:1][C@@H:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4])=[O:20]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 19066320Pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoateHCID 54357909(S)-alpha-amino-p-carboxymethylphenylacetic acid

生成物 1

HCID 15294191(2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid収率 64%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 22242641Methanol--water (1/1)溶媒

実験手順

To a solution of (S)-α-amino-p-carboxymethylphenylacetic acid (0.1 g, 0.48 mmol) and pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzoate (0.213 g, 0.4 mmol), prepared as described in Example 2, in 5 ml of DMF was added bistrimethyl silyl acetamide (BSA) (0.194 g, 0.96 mmol). After stirring under N2 for 20 minutes N-methylmorpholine was added (0.081 g, 0.8 mmol) followed by N-hydroxybenzotriazole (HOBT) (0.01 g). The reaction mixture was stirred at room temperature for 4 hours and evaporated to dryness. The solid obtained by trituration with ether and filtration was resuspended in a mixture of methanol/water (2 ml) and the pH adjusted to 2.5 with 2N HCl . The resulting precipitate was filtered off, washed with water and dried to give (2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid (140 mg, 64%) as a yellow solid;

後処理

  1. additionwas added (0.081 g, 0.8 mmol)
  2. customevaporated to dryness
  3. customThe solid obtained by trituration with ether and filtration
  4. filtrationThe resulting precipitate was filtered off
  5. washwashed with water
  6. customdried

出典と根拠

ORDレコード
ord-bf319897378e4a9aa44c6c885a643c6d
出典データセット
uspto-grants-1998_05
特許番号
US05747499

反応ノート

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