Hydrochloric Acid → HCID 86712732, compound

HRID 1779099Notes

Reaction equation

HRID 1779099 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][CH:43]([N:46]2[CH:50]=[C:49]([NH:51][C:52]3[N:57]=[C:56]([CH2:58][CH2:59][C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=4[CH2:66][C:67]([OH:69])=O)[C:55]([CH3:70])=[CH:54][N:53]=3)[CH:48]=[N: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:67](=[O:69])[CH2:66][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=1[CH2:59][CH2:58][C:56]1[C:55]([CH3:70])=[CH:54][N:53]=[C:52]([NH:51][C:49]2[CH:48]=[N:47][N:46]([CH: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:50]=2)[N:57]=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 86712731HCID 86712731, compound

Product 1

HCID 86712732HCID 86712732, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HOBt (0.051 g, 0.379 mmol), EDCl.HCl (0.081 g, 0.42 mmol) and DIPEA (0.11 mL, 0.65 mmol) were added to a solution of 2-(2-(2-(2-((1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylpyrimidin-4-ylethyl)phenyl)acetic acid (A127) (0.068 g, 0.131 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (0.126 g, 1.31 mmol) was added in one portion and the resulting mixture stirred for 18 hours at room temperature. Additional HOBt (0.051 g, 0.38 mmol), EDCl.HCl (0.081 g, 0.42 mmol), DIPEA (0.11 mL, 0.65 mmol) and ammonium carbonate (0.126 g, 1.31 mmol) were added to the reaction mixture and the mixture stirred for 12 days at room temperature. The volatiles were removed in vacuo then the residue diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine (25 mL) and dried over Na2SO4. The solvent was removed in vacuo to afford a yellow oil that was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-30% MeOH in EtOAc) to give the title compound A127 as an off white solid (0.044 g, 65%); 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.85 (s, 1H), 7.50 (d, J=0.5 Hz, 1H), 7.26-7.17 (m, 5H), 5.79 (s, 1H), 5.62 (s, 1H), 4.26-4.19 (m, 3H), 3.65 (s, 2H), 3.07 (dd, J=9.5, 6.2 Hz, 2H), 2.93-2.82 (m, 4H), 2.15-2.08 (m, 2H), 2.04 (s, 3H), 1.91 (qd, J=12.3, 4.3 Hz, 2H), 1.46 (s, 9H). LCMS-A: rt 5.178 min; m/z 520 [M+H]+.

Workup

  1. stirringthe mixture stirred for 12 days at room temperature
  2. customThe volatiles were removed in vacuo
  3. additionthe residue diluted with EtOAc (50 mL)
  4. washwashed with saturated aqueous NaHCO3 (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×25 mL)
  6. washThe combined organic layers were washed with brine (25 mL)
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed in vacuo
  9. customto afford a yellow oil that
  10. customwas purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-f17dd0ec912248d98a3aa3032e0f0f36
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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