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

HRID 1013484
Notes
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Reaction equation

HRID 1013484 reaction equation
[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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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+)

Workup

  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

Sources & evidence

ORD record
ord-10c6ac46e7ec4ff4a2c5da285395153c
Source dataset
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07981874B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes