1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68282576, compound

HRID 1473161Notes

Reaction equation

HRID 1473161 reaction equation
O[N:2]1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.C(N(CC)C(C)C)(C)C.C(OC([N:38]1[CH2:42][CH2:41][CH:40]([C:43]2[CH:48]=[CH:47][C:46]([NH:49][C:50]3[N:55]=[C:54]([CH2:56][CH2:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=4[CH2:64][C:65]([O-:67])=O)[C:53]([C:68]([F:71])([F:70])[F:69])=[CH:52][N:51]=3)=[CH:45][CH:44]=2)[CH2:39]1)=O)(C)(C)C.[Li+].C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH:38]1[CH2:42][CH2:41][CH:40]([C:43]2[CH:44]=[CH:45][C:46]([NH:49][C:50]3[N:55]=[C:54]([CH2:56][CH2:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=4[CH2:64][C:65]([NH2:2])=[O:67])[C:53]([C:68]([F:71])([F:70])[F:69])=[CH:52][N:51]=3)=[CH:47][CH:48]=2)[CH2:39]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 68282864HCID 68282864, compound

Product 1

HCID 68282576HCID 68282576, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Hydroxybenzotriazole (38.0 mg, 0.28 mmol), EDCI (50.0 mg, 0.32 mmol) and N,N-diisopropylethylamine (187 uL, 1.08 mmol) were added to a solution of lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I140) (124 mg, 0.215 mmol) in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. Ammonium carbonate (101 mg, 1.08 mmol) was added in one portion to the stirred reaction mixture after 10 minutes and the reaction was stirred at room temperature for 23 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (65 mL) and washed with saturated NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL) and dried over MgSO4. The solvent was removed in vacuo to afford a pale yellow oil. The crude material was purified by column chromatography on silica gel (0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I141) (76 mg, 62%) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 8.02 (s, 1H), 7.56 (d, J=7.4 Hz, 2H), 7.29-7.20 (m, 4H, obscured by solvent), 5.36 (d, J=21.2 Hz, 2H), 3.89-3.76 (m, 1H), 3.66-3.51 (m, 2H), 3.45-3.27 (m, 4H), 3.15-3.04 (m, 4H), 2.29-2.25 (m, 1H), 2.01-1.94 (m, 1H), 1.49 (s, 9H). LCMS Method C: rt 6.37 min; m/z 570.1 [M+H]+, 568.2 [M−H]−.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residual solution was diluted with EtOAc (65 mL)
  3. washwashed with saturated NaHCO3 (65 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed in vacuo
  8. customto afford a pale yellow oil
  9. customThe crude material was purified by column chromatography on silica gel (0-80% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-8c0939ad79f54452a6b7f72e4091ba6e
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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