Hydrochloric Acid → HCID 86706479, compound

HRID 919621Notes

Reaction equation

HRID 919621 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.Cl.CCN(C(C)C)C(C)C.[F:34][C:35]([F:50])([F:49])[C:36]([NH:38][CH:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][NH:41][CH2:40]1)=[O:37]>CN(C=O)C.CCOC(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([NH:9][CH2:10][C:11]([N:41]2[CH2:40][CH:39]([NH:38][C:36](=[O:37])[C:35]([F:50])([F:34])[F:49])[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:13])[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 121205692,2,2-Trifluoro-N-(1,2,3,4-tetrahydroisoquinolin-4-yl)acetamideHCID 13138167(3,5-Dichlorophenyl)glycine

Product 1

HCID 86706479HCID 86706479, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3,5-dichlorophenylamino)acetic acid (0.332 g, 1.5 mmol) in DMF (10 mL) was added HOBt (0.30 g, 2.2 mmol) EDCI: HCl (0.434 g, 2.2 mmol), DIEA (0.39 g, 3.0 mmol) and 2,2,2-trifluoro-N-(1,2,3,4-tetrahydroisoquinolin-4-yl)acetamide (370 mg, 1.5 mmol) at 0° C. The reaction mixture was warmed to rt and stirred overnight. After the reaction was shown to be complete as indicated by TLC the reaction mixture was diluted with EtOAc (50 mL), and washed with water (20 mL×3). The EtOAc layer was concentrated in vacuo to give crude reaction mixture which was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to give (0.45 g, 74%) of the titled intermediate. 1H NMR (DMSO-d6, 400 MHz): δ 7.56 (s, 1H), 7.37-7.21 (m, 4H), 6.74 (d, J=11.6 Hz, 2H), 6.61 (s, 1H), 6.4-6.2 (m, 1H), 5.20-5.06 (m, 1H), 4.85 (t, J=16.4 Hz, 1H), 4.60 (d, J=16.8 Hz, 1H), 4.58 (d, J=17.6, 1 H), 4.12-4.03 (m, 1H), 3.9-3.8 (m, 1H), 3.58-3.39 (m, 1H). LCMS: M/z: (M+1):446

Workup

  1. customat 0° C
  2. washwashed with water (20 mL×3)
  3. concentrationThe EtOAc layer was concentrated in vacuo
  4. customto give crude
  5. customreaction mixture which
  6. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9fc5f1c0b4b84df488bc8b208f04aaac
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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