Hydrochloric Acid → HCID 86712685, compound

HRID 1779037Notes

Reaction equation

HRID 1779037 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[C:24]([O:28][C:29]([N:31]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]2[N:48]=[C:47]([CH2:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=3[CH2:57][C:58]([OH:60])=O)[C:46]([C:61]([F:64])([F:63])[F:62])=[CH:45][N:44]=2)=[CH:38][CH:37]=1)[CH2:32][CH2:33][OH:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].CCN(CC)CC.C(=O)([O-])[O-].[NH4+].[NH4+].C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:7][C:58](=[O:60])[CH2:57][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=1[CH2:50][CH2:49][C:47]1[C:46]([C:61]([F:64])([F:62])[F:63])=[CH:45][N:44]=[C:43]([NH:42][C:39]2[CH:40]=[CH:41][C:36]([CH2:35][N:31]([CH2:32][CH2:33][OH:34])[C:29](=[O:30])[O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:37][CH:38]=2)[N:48]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712684HCID 86712684, compound

Product 1

HCID 86712685HCID 86712685, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

HOBt (0.119 g, 0.879 mmol) and EDCl.HCl (0.169 g, 0.879 mmol) were added to a solution of 2-(2-(2-(2-((4-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A74) (0.421 g, 0.733 mmol) and Et3N (0.408 mL, 0.297 mmol) in DMF (10 mL). After 10 minutes ammonium carbonate (1.34 g, 14.65 mmol) was added and the resulting mixture was stirred at 40° C. for 22 hours. Saturated aqueous saturated NaHCO3 solution (25 mL) was added the resulting mixture extracted with EtOAc (3×15 mL). The combined organic fractions were dried (Na2SO4), filtered and evaporated in vacuo. The residue was adsorbed onto silica gel then purified using column chromatography (CombiFlash Rf, 24 g SiO2 cartridge, 40-100% EtOAc in cyclohexane) to give the title compound A75 as a white solid (0.301 g, 76%); 1H NMR (300 MHz, CDCl3) δ 8.56 (s, 1H), 7.61-7.58 (m, 3H), 7.30-7.26 (m, 6H), 5.48 (brs, 2H), 4.49 (brs, 2H), 3.74 (brs, 4H), 3.42 (brs, 2H), 3.15-3.12 (m, 4H), 1.50 (s, 9H). LCMS-B: rt 7.344 min; m/z 574 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. dry with materialThe combined organic fractions were dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customthen purified

Sources & evidence

ORD record
ord-1f2dba86446d451495312846b65abd98
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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