Potassium Carbonate → HCID 178502435, 화합물

HRID 1625517노트

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HRID 1625517 반응식
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]

참가 물질

10

반응물 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, 화합물HCID 178502434HCID 178502434, 화합물HCID 178502451HCID 178502451, 화합물

생성물 1

HCID 178502435HCID 178502435, 화합물

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 3776Isopropanol용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4d1d18a28067417696f2c0d6d504d5c2
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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