Potassium Carbonate → HCID 178502435、化合物

HRID 1625517ノート

反応式

HRID 1625517 の反応式
I[C:2]1[N:3]=[C:4]([C@@H:7]2[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]2[C:13]([C@@H:15]([NH:19][C:20](=[O:23])[O:21][CH3:22])[CH:16]([CH3:18])[CH3:17])=[O:14])[NH:5][CH:6]=1.I[C:25]1[CH:50]=[CH:49][C:28]2[NH:29][C:30]([C@@H:32]3[CH2:36][C@H:35]([CH3:37])[CH2:34][N:33]3[C:38]([C@@H:40]([NH:44][C:45](=[O:48])[O:46][CH3:47])[CH:41]([CH3:43])[CH3:42])=[O:39])=[N:31][C:27]=2[CH:26]=1.CC1(C)C(C)(C)OB([C:59]2[S:63][C:62]3[CH:64]=[C:65](B4OC(C)(C)C(C)(C)O4)[S:66][C:61]=3[CH:60]=2)O1.C([O-])([O-])=O.[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=C(S(O[Na])(=O)=O)C=CC=2OC)CCCCC1>C(O)(C)C.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:47][O:46][C:45]([NH:44][C@@H:40]([CH:41]([CH3:43])[CH3:42])[C:38]([N:33]1[CH2:34][C@@H:35]([CH3:37])[CH2:36][C@H:32]1[C:30]1[NH:29][C:28]2[CH:49]=[CH:50][C:25]([C:65]3[S:66][C:61]4[CH:60]=[C:59]([C:2]5[N:3]=[C:4]([C@@H:7]6[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]6[C:13]([C@@H:15]([NH:19][C:20](=[O:23])[O:21][CH3:22])[CH:16]([CH3:18])[CH3:17])=[O:14])[NH:5][CH:6]=5)[S:63][C:62]=4[CH:64]=3)=[CH:26][C:27]=2[N:31]=1)=[O:39])=[O:48]

参加物

10

反応物 5

HCID 11430Potassium CarbonateHCID 588254992,5-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[3,2-b]thiopheneHCID 178492906HCID 178492906、化合物HCID 178502434HCID 178502434、化合物HCID 178502451HCID 178502451、化合物

生成物 1

HCID 178502435HCID 178502435、化合物

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a degassed (vacuum/nitrogen flush) mixture of methyl N-[(1S)-1-[(2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (153.5 mg, 0.3347 mmol), methyl N-[(1S)-1-[(2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (162.1 mg, 0.3347 mmol), 4,4,5,5-tetramethyl-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[3,2-b]thiophen-2-yl]-1,3,2-dioxaborolane (125 mg, 0.3188 mmol) and K2CO3 (220.3 mg, 1.594 mmol) in degassed isopropanol (3.750 mL) and H2O (1.250 mL) are added [3-(2-dicyclohexylphosphanylphenyl)-2,4-dinnethoxy-phenyl]sulfonyloxysodium (VPHOS) (13.07 mg, 0.02550 mmol) and Pd(OAc)2 (1.431 mg, 0.006376 mmol). After degassing twice, reaction mixture is heated at 90° C. for 16 hours, then diluted with ethyl acetate (30 mL). The aqueous solution is discarded, and the organic solution is washed with water, brine, dried (Na2SO4) and concentrated. The residue is purified by silica gel chromatography using ethyl acetate to 8% MeOH-EtOAc as eluent to afford a mixture of products (160 mg) as yellow solid. The desired compound is isolated by reverse phase preparative HPLC to afford methyl N-[(1S)-1-[(2S,4S)-2-[4-[5-[2-[(2S,4S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]thieno[3,2-b]thiophen-2-yl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (34.4 mg) as yellow solid.

後処理

  1. customTo a degassed
  2. customAfter degassing twice
  3. customreaction mixture
  4. washthe organic solution is washed with water, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography
  8. customto afford

出典と根拠

ORDレコード
ord-4d1d18a28067417696f2c0d6d504d5c2
出典データセット
uspto-grants-2014_07
特許番号
US08779156B2

反応ノート

読み込み中…