1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178466651, compound

HRID 475701Notes

Reaction equation

HRID 475701 reaction equation
[CH:1]1([NH:4][C@H:5]2[CH2:10][CH2:9][C@H:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[F:17][C:18]([F:32])([F:31])[C@:19]([C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)([OH:21])[CH3:20].CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:1]1([N:4]([C@H:5]2[CH2:6][CH2:7][C@H:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH2:9][CH2:10]2)[C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([C@@:19]([OH:21])([CH3:20])[C:18]([F:17])([F:31])[F:32])=[CH:23][CH:24]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 57892515(S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acidHCID 178420786HCID 178420786, compound

Product 1

HCID 178466651HCID 178466651, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

trans-N-cyclopropyl-4-(pyridine-3-yl)cyclohexylamine (7.3 g, 34.0 mmol, prepared as described above), (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid (8.7 g, 37.3 mmol), EDCI (9.1 g, 47.6 mmol), HOAt (6.5 g, 47.6 mmol), and NaHCO3 (5.7 g, 68.0 mmol) were combined and dissolved in DMF (125 mL). After being stirred for 16 h at 23° C., the reaction was quenched with 1 M NaOH (150 mL) and diluted with EtOAc (300 mL). The aqueous layer was extracted with EtOAc (100 mL) and 10% MeOH/CH2Cl2 (5×100 mL) and the combined organic layers were washed with H2O (400 mL) and brine (400 mL), dried with MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (gradient elution, 3%→10% MeOH/CH2Cl2) to afford the product: 1H NMR (CDCl3, 500 MHz) δ 8.49 (s, 1H), 8.46 (d, J=3.6 Hz, 1H), 7.61 (d, J=8.1 Hz, 2H), 7.58 (d, J=7.7 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.24 (dd, 1H-overlapping with CDCl3), 4.23 (m, 1H), 2.80 (m, 1H), 2.62 (m, 2H), 2.05 (m, 6H), 1.80 (s, 3H), 1.65 (m, 2H), 0.60 (d, J=4.8 Hz, 2H), 0.49 (m, 2H); MS(ESI) 433.3 [M+H]+; Anal. (C24H27F3N2O2) C, H, N.

Workup

  1. customthe reaction was quenched with 1 M NaOH (150 mL)
  2. additiondiluted with EtOAc (300 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (100 mL) and 10% MeOH/CH2Cl2 (5×100 mL)
  4. washthe combined organic layers were washed with H2O (400 mL) and brine (400 mL)
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash column chromatography (gradient elution, 3%→10% MeOH/CH2Cl2)
  9. customto afford the product

Sources & evidence

ORD record
ord-86b1bfff888c4c8ba5ef5c8f46556967
Source dataset
uspto-grants-2014_01
Patent number
US08637576B2

Reaction notes

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