1,2-Dichloroethane → HCID 25011833, compound

HRID 1013487Notes

Reaction equation

HRID 1013487 reaction equation
C(OC([NH:8][CH:9]([P:19]([O:23][CH3:24])([O:21][CH3:22])=[O:20])[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)=O)(C)(C)C.C(OC(=O)[NH:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:39][CH:40]=[CH:41][CH:42]=2)=[CH:34][C:33]=1[NH2:43])(C)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:24][O:23][P:19]([CH:9]([NH2:8])[C:10]1[CH:11]=[CH:12][C:13]([C:14](=[O:16])[NH:43][C:33]2[CH:34]=[C:35]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)[CH:36]=[CH:37][C:32]=2[NH2:31])=[CH:17][CH:18]=1)(=[O:20])[O:21][CH3:22]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 57925948HCID 57925948, compound

Product 1

HCID 25011833HCID 25011833, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[tert-Butoxycarbonylamino-(dimethoxy-phosphoryl)-methyl]-benzoic acid (76 mg, 0.212 mmol), (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester (74 mg, 0.254 mmol), EDC (61 mg, 0.317 mmol), HOBT (39 mg, 0.254 mmol), and DIPEA (82 mg, 0.635 mmol) were combined and diluted with DMF (0.85 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 identified, combined, then concentrated in vacuo. The residue was diluted with 10:1 DCM:TFA and stirred at ambient temperature. After 2 h the mixture was concentrated in vacuo to give the title compound: 1H NMR (DMSO-d6, 600 MHz) 9.81 (s, 1H), 9.06 (br-s, 2H), 8.05 (d, J=9.0 Hz, 2H), 7.62 (d, J=9.0 Hz, 2H), 7.44-7.46 (m, 1H), 7.34-7.36 (m, 1H), 7.29-7.32 (m, 1H), 7.22-7.24 (m, 1H), 7.03-7.05 (m, 1H), 6.82 (d, J=7.8 Hz, 2H), 5.20 (d, J=17.4 Hz, 1H), 3.73 (d, J=10.8 Hz, 3H), 3.58 (d, J=10.8 Hz, 3H). MS: cal'd 432 (MH+), exp 432 (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. concentrationAfter 2 h the mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-8150fe1fbb0c413593f99b9355757b8b
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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