Triethylamine → N-[(3S*,4S*)-4-(3-Benzyl-1-cyclopropyl-ureidomethyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

HRID 1158432ノート

反応式

HRID 1158432 の反応式
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][N:35]([CH:46]2[CH2:48][CH2:47]2)[C:36]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37])[CH2:9]1)=O)(C)(C)C.C(OC(N1C[C@@H](CN(C(C)C)C(=O)C2C=CC(OC)=C(OCCCOC)C=2)[C@H](CNC2CC2)C1)=O)(C)(C)C.C(N(CC)CC)C.C(N=C=O)C1C=CC=CC=1>C1COCC1.O>[CH2:39]([NH:38][C:36](=[O:37])[N:35]([CH2:34][C@@H:10]1[CH2:9][NH:8][CH2:12][C@H:11]1[CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=1)[CH:46]1[CH2:47][CH2:48]1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 76639Benzyl isocyanateHCID 68616408(3R*,4R*)-3-Cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 68616937(3R*,4R*)-3-(3-Benzyl-1-cyclopropyl-ureidomethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 59512259N-[(3S*,4S*)-4-(3-Benzyl-1-cyclopropyl-ureidomethyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

(3R*,4R*)-3-(3-Benzyl-1-cyclopropyl-ureidomethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl Ester To a solution of ((3R*,4R*)-3-cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (235 mg, 0.440 mmol) in THF (6 mL) is added triethylamine (123 μL, 0.880 mmol) followed by benzylisocyanate (54 μL, 0.440 mmol). The mixture is stirred at RT for 2 h before water is added. Extraction with ethyl acetate, drying of the combined extracts (Na2SO4), filtration and evaporation of the solvent affords the crude product which is purified by flash chromatography on silica gel (eluent gradient: CH2Cl2 100% to CH2Cl2/MeOH 9:1) to give the title compound. MS (LC-MS): 667.1M+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 6.26 min.

後処理

  1. additionis added
  2. extractionExtraction with ethyl acetate
  3. dry with materialdrying of the combined extracts (Na2SO4), filtration and evaporation of the solvent
  4. customaffords the crude product which
  5. customis purified by flash chromatography on silica gel (eluent gradient: CH2Cl2 100% to CH2Cl2/MeOH 9:1)

出典と根拠

ORDレコード
ord-88bfeeca94554769b8f5c11deacc0b2f
出典データセット
uspto-grants-2010_10
特許番号
US07807709B2

反応ノート

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