Hydrochloric Acid → HCID 86712637, compound

HRID 1778965Notes

Reaction equation

HRID 1778965 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CCN(C(C)C)C(C)C.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][N:43]([C:46]2[CH:51]=[CH:50][C:49]([NH:52][C:53]3[N:58]=[C:57]([CH2:59][CH2:60][C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=4[CH2:67][C:68]([OH:70])=O)[C:56]([CH3:71])=[CH:55][N:54]=3)=[CH:48][CH:47]=2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[NH4+].[NH4+]>CN(C=O)C>[NH2:7][C:68](=[O:70])[CH2:67][C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=1[CH2:60][CH2:59][C:57]1[C:56]([CH3:71])=[CH:55][N:54]=[C:53]([NH:52][C:49]2[CH:50]=[CH:51][C:46]([N:43]3[CH2:44][CH2:45][N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:39])[CH2:41][CH2:42]3)=[CH:47][CH:48]=2)[N:58]=1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 517111Ammonium Carbonate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 86712636HCID 86712636, compound

Product 1

HCID 86712637HCID 86712637, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

HOBt (15 mg, 0.11 mmol), EDCl.HCl (21 mg, 0.11 mmol) and DIPEA (72 μL, 0.41 mmol) were added to a solution of 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)acetic acid (A9) (44 mg, 0.083 mmol) in dry DMF (10 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (40 mg, 0.41 mmol) was added and the resulting mixture was stirred at room temperature for 18 hours. A solution of HOBt (15 mg, 0.11 mmol), EDCl.HCl (21 mg, 0.11 mmol) and DIPEA in DMF (3 mL) was then added and after 10 minutes ammonium carbonate (40 mg, 0.41 mmol) was added in one portion. The resulting mixture was stirred at 26° C. for a further 24 hours before the volatiles were removed in vacuo and the residue partitioned between EtOAc (65 mL) and saturated NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organics were washed with brine (50 mL) and dried over Na2SO4. After filtration the solvent was removed in vacuo to afford a pale yellow solid which was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-100% MeOH in EtOAc). After removing the solvent in vacuo the resulting residue was taken up in EtOAc, filtered through cotton wool and the filtrate evaporated to dryness to give the title compound A10 as a light brown solid (28 mg, 64%); 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.47-7.41 (m, 2H), 7.25-7.17 (m, 4H), 7.13 (s, 1H), 6.93-6.88 (m, 2H), 5.59 (s, 1H), 5.53 (s, 1H), 3.65 (s, 2H), 3.61-3.55 (m, 4H), 3.10-3.01 (m, 6H), 2.92-2.88 (m, 2H), 2.08 (s, 3H), 1.48 (s, 9H). LCMS-A: rt 5.525 min; m/z 531.2 [M+H]+

Workup

  1. additionwas added in one portion
  2. stirringThe resulting mixture was stirred at 26° C. for a further 24 hours before the volatiles
  3. customwere removed in vacuo
  4. customthe residue partitioned between EtOAc (65 mL) and saturated NaHCO3 (65 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washthe combined organics were washed with brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration the solvent
  9. customwas removed in vacuo
  10. customto afford a pale yellow solid which
  11. custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.
  12. customAfter removing the solvent in vacuo the resulting residue
  13. filtrationfiltered through cotton wool
  14. customthe filtrate evaporated to dryness

Sources & evidence

ORD record
ord-e8f22eb0d41241008e1a19780b84cdb5
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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