Lithium Hydroxide → HCID 58355815, 화합물

HRID 39315

반응식

HRID 39315 반응식
C[O:2][C:3]([C:5]1[S:6][C:7]([C:25]#[C:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:8][C:9]=1[N:10]([C:16]([CH:18]1[CH2:23][CH2:22][CH:21]([CH3:24])[CH2:20][CH2:19]1)=[O:17])[CH:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)=[O:4].Cl.[N:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1C(Cl)=O.CCN(C(C)C)C(C)C.[C:50]([O-])(O)=[O:51].[Na+].[OH-].[Li+]>C(Cl)Cl.[Cl-].[Na+].O.O.CO>[CH3:29][C:27]([CH3:28])([CH3:30])[C:26]#[C:25][C:7]1[S:6][C:5]([C:3]([OH:2])=[O:4])=[C:9]([N:10]([C:16]([CH:18]2[CH2:19][CH2:20][CH:21]([CH3:24])[CH2:22][CH2:23]2)=[O:17])[CH:11]2[CH2:15][CH2:14][N:13]([C:50]([C:36]3[CH:37]=[N:32][CH:33]=[CH:34][CH:35]=3)=[O:51])[CH2:12]2)[CH:8]=1

참가 물질

10

반응물 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 135033Picolinoyl Chloride HydrochlorideHCID 516892Sodium BicarbonateHCID 58355783HCID 58355783, 화합물

생성물 1

HCID 58355815HCID 58355815, 화합물

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 57417360Sodium chloride; water용매

실험 절차

A mixture of 5-(3,3-Dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohexanecarbonyl)-pyrrolidin-3-yl-amino]-thiophene-2-carboxylic acid methyl ester (74 mg, 0.158 mmol) and pyridine-2-carbonyl chloride HCl salt (56 mg, 0.31 mmol) in DCM (2 mL) was treated with DIEA (124 μL, 0.8 mmol). After 30 min, NaHCO3 (saturated aqueous solution, 4-8 mL) was added to the mixture, followed by brine (20 mL), and the crude product was extracted with ethyl acetate (2×20 mL). The combined organic layers were concentrated and the crude material was dissolved in a 3:2:1 mixture of THF:MeOH:water (5 mL), treated with lithium hydroxide (42 mg, 1 mmol,) and heated to 60 deg C. for 2 hours. The residue was purified by HPLC (Gemini column, 35% acetonitrile:water, 2 min, 35-50% acetonitrile:water, 2 min, 50-100% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid). This resulted in 37 mg of the title compound as its TFA salt: MS (m/z): 522.0 [M−H]+; HPLC retention time: 3.58 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

후처리

  1. extractionthe crude product was extracted with ethyl acetate (2×20 mL)
  2. concentrationThe combined organic layers were concentrated
  3. dissolutionthe crude material was dissolved in a 3:2:1 mixture of THF
  4. temperatureheated to 60 deg C
  5. waitfor 2 hours
  6. customThe residue was purified by HPLC (Gemini column, 35% acetonitrile
  7. additionwater, 2 min, 35-50% acetonitrile:water, 2 min, 50-100% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-7e65982abbcd4529b58a190e121e1e40
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524764B2

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