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Methyl chloroformate → (S)-methyl 1-(4-(4-(2-chloro-3-(propylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

HRID 535772
ノート
印刷プレビュー

反応式

HRID 535772 の反応式
[NH2:1][C@@H:2]([CH3:33])[CH2:3][NH:4][C:5]1[N:10]=[C:9]([C:11]2[NH:15][C:14]([CH:16]3[CH2:18][CH2:17]3)=[N:13][C:12]=2[C:19]2[C:20]([Cl:32])=[C:21]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:8]=[CH:7][N:6]=1.C([O-])(O)=O.[Na+].Cl[C:40]([O:42][CH3:43])=[O:41]>C1COCC1.O.O>[Cl:32][C:20]1[C:21]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])=[CH:22][CH:23]=[CH:24][C:19]=1[C:12]1[N:13]=[C:14]([CH:16]2[CH2:18][CH2:17]2)[NH:15][C:11]=1[C:9]1[CH:8]=[CH:7][N:6]=[C:5]([NH:4][CH2:3][C@@H:2]([NH:1][C:40](=[O:41])[O:42][CH3:43])[CH3:33])[N:10]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 6586Methyl chloroformateHCID 516892Sodium BicarbonateHCID 69809521(S)-N-(3-(5-(2-(2-aminopropylamino)pyrimidin-4-yl)-2-cyclopropyl-1H-imidazol-4-yl)-2-chlorophenyl)propane-1-sulfonamide

生成物 1

HCID 58164470(S)-methyl 1-(4-(4-(2-chloro-3-(propylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

試薬・触媒・溶媒 2

HCID 962
Water
溶媒
HCID 21881883Oxolane--water (1/1)溶媒

実験手順

To a mixture of (S)—N-(3-(5-(2-(2-aminopropylamino)pyrimidin-4-yl)-2-cyclopropyl-1H-imidazol-4-yl)-2-chlorophenyl)propane-1-sulfonamide in THF-water (1:1, 2 mL) at 0° C. was added solid NaHCO3 (137 mg, 1.6 mmol) and the resulting mixture was stirred for 5 minutes. Methyl chloroformate (14 μL, 0.18 mmol) was added and the reaction mixture was stirred at 0° C. for 15 minutes. The reaction was diluted with water and extracted with EtOAc (2×). The combined organic portions were washed with water, brine, dried (Na2SO4), and concentrated. The resulting residue was dissolved in DMSO and purified by reverse phase HPLC. Product fractions were combined and lyophilized to give (S)-methyl 1-(4-(4-(2-chloro-3-(propylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (19.9 mg) as the TFA salt (4A-3): LCMS (m/z) 548.0 (MH+), tR=0.61 minute, 1H NMR (400 MHz, CD3OD) δ 1.04 (t, J=7.4 Hz, 3H) 1.14 (d, J=6.6 Hz, 3H) 1.27 (t, J=4.5 Hz, 2H) 1.34-1.44 (m, 2H) 1.80-1.95 (m, 2H) 3.14-3.21 (m, 2H) 3.67 (br s, 3H) 3.97 (br s, 1H) 6.40 (br s, 1H) 7.45 (d, 7.0 Hz, 1H) 7.54 (m, 1H) 7.84 (d, J=7.4 Hz, 1H) 8.13 (d, J=5.1 Hz, 1H).

後処理

  1. stirringthe reaction mixture was stirred at 0° C. for 15 minutes
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic portions were washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in DMSO
  7. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-a2775c72c2044286b5ac8333d20a321a
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08859548B2

反応ノート

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