1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → methyl 2-(4-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carbonyl)hydrazinecarbodithioate

HRID 1408988

反応式

HRID 1408988 の反応式
[C:1]([O:5][C:6]([NH:8][C@@:9]1([CH3:32])[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]2[C:16]3[N:17]([CH:24]=[C:25]([C:27](O)=[O:28])[CH:26]=3)[N:18]=[CH:19][C:20]=2[C:21](=[O:23])[NH2:22])[C:10]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH:63]([C:65]([S:67][CH3:68])=[S:66])[NH2:64]>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][C@@:9]1([CH3:32])[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]2[C:16]3[N:17]([CH:24]=[C:25]([C:27]([NH:64][NH:63][C:65]([S:67][CH3:68])=[S:66])=[O:28])[CH:26]=3)[N:18]=[CH:19][C:20]=2[C:21](=[O:23])[NH2:22])[C:10]1([CH3:30])[CH3:31])=[O:7])([CH3:2])([CH3:4])[CH3:3]

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 3034069MethyldithiocarbazateHCID 867077164-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid

生成物 1

HCID 86707721methyl 2-(4-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carbonyl)hydrazinecarbodithioate収率 76%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 4-((1R,3S)-3-(tert-butoxycarbonylamino)-2,2,3-trimethylcyclopentylamino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid (500 mg, 1.122 mmol, from Step 3 of Example 346). HOBT (206 mg, 1.347 mmol) and DIEA (0.490 mL, 2.81 mmol) in DMF (4 mL) were added EDCI (280 mg, 1.459 mmol) and methyl hydrazinecarbodithioate (144 mg, 1.178 mmol) at 23° C. The reaction mixture was stirred for 1.5 hrs followed by the addition of 25 mL of water. The solids were removed. The water phase was extracted with EtOAc (2×30 mL). The combined organic phase was washed with 10% LiCl solution (2×20 mL), 20 mL of brine and dried over Na2SO4. Filtration and concentration gave methyl 2-(4-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carbonyl)hydrazinecarbodithioate (466.5 mg, 76% yield). MS (ES+) m/z: 550.08 (M+H); HPLC retention time: 3.168 min (analytical HPLC Method F).

後処理

  1. customThe solids were removed
  2. extractionThe water phase was extracted with EtOAc (2×30 mL)
  3. washThe combined organic phase was washed with 10% LiCl solution (2×20 mL), 20 mL of brine
  4. dry with materialdried over Na2SO4
  5. filtrationFiltration and concentration

出典と根拠

ORDレコード
ord-8621e466c6124edd82b79cd0b0ff187b
出典データセット
uspto-grants-2014_12
特許番号
US08921368B2

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