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1,2-Dichloroethane → {[4-(2-Amino-5-thiophen-2-yl-phenylcarbamoyl)-phenyl]-fluoro-methyl}-phosphonic acid dimethyl ester

HRID 1013484
ノート
印刷プレビュー

反応式

HRID 1013484 の反応式
[CH3:1][O:2][P:3]([CH:7]([F:17])[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)([O:5][CH3:6])=[O:4].C(OC(=O)[NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[S:32][CH:33]=[CH:34][CH:35]=2)=[CH:27][C:26]=1[NH2:36])(C)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:6][O:5][P:3]([CH:7]([C:8]1[CH:9]=[CH:10][C:11]([C:12](=[O:14])[NH:36][C:26]2[CH:27]=[C:28]([C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)[CH:29]=[CH:30][C:25]=2[NH2:24])=[CH:15][CH:16]=1)[F:17])(=[O:4])[O:2][CH3:1]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 579258224-[(Dimethoxy-phosphoryl)-fluoro-methyl]-benzoic acid

生成物 1

HCID 25014349
{[4-(2-Amino-5-thiophen-2-yl-phenylcarbamoyl)-phenyl]-fluoro-methyl}-phosphonic acid dimethyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

4-[(Dimethoxy-phosphoryl)-fluoro-methyl]-benzoic acid (52 mg, 0.198 mmol), (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester (69 mg, 0.238 mmol), EDC (57 mg, 0.298 mmol), HOBT (36 mg, 0.238 mmol), and DIPEA (77 mg, 0.595 mmol) were combined and diluted with DMF (0.79 mL). The resulting mixture was stirred at ambient temperature for 18 hours. The reaction mixture was purified directly by HPLC (20-85% MeCN in water w/0.025% TFA). Pure fractions were combined and concentrated in vacuo. The residue was diluted with 10:1 DCM:TFA and stirred at ambient temperature. After 2 hours the deprotection was complete and the mixture was concentrated in vacuo to give the title compound: 1H NMR (DMSO-d6, 600 MHz) δ 9.87 (br-s, 1H), 8.05 (d, J=8.4 Hz, 2H), 7.56 (d, J=7.8 Hz, 2H), 7.48 (s, 1H), 7.37 (d, J=5.0 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.24-7.27 (m, 1H), 7.04 (dd, J=3.6 Hz, J=5.0 Hz, 1H), 6.86 (d, J=8.4 Hz, 1H), 6.33 (dd, J=8.4 Hz, J=43.8 Hz, 1H), 3.64-3.71 (m, 6H). MS: cal'd 435 (MH+), exp 435 (MH+)

後処理

  1. customThe reaction mixture was purified directly by HPLC (20-85% MeCN in water w/0.025% TFA)
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with 10:1 DCM
  4. stirringTFA and stirred at ambient temperature
  5. waitAfter 2 hours the deprotection was complete
  6. concentrationthe mixture was concentrated in vacuo

出典と根拠

ORDレコード
ord-10c6ac46e7ec4ff4a2c5da285395153c
出典データセット
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07981874B2

反応ノート

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