Hydrochloric Acid → HCID 86712630, compound

HRID 1778960Notes

Reaction equation

HRID 1778960 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH2:24]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([NH:46][C:47]3[N:52]=[C:51]([CH2:53][CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=4[CH2:61][C:62]([OH:64])=O)[CH:50]=[CH:49][N:48]=3)=[CH:42][CH:41]=2)[CH2:36][CH2:35]1)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH2:7][C:62](=[O:64])[CH2:61][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=1[CH2:54][CH2:53][C:51]1[CH:50]=[CH:49][N:48]=[C:47]([NH:46][C:43]2[CH:44]=[CH:45][C:40]([N:37]3[CH2:36][CH2:35][N:34]([C:32]([O:31][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:33])[CH2:39][CH2:38]3)=[CH:41][CH:42]=2)[N:52]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712631HCID 86712631, compound

Product 1

HCID 86712630HCID 86712630, compoundYield 97.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

HOBt (24 mg, 0.17 mmol), EDCl.HCl (33 mg, 0.17 mmol) and DI PEA (0.12 mL, 0.67 mmol) were added to a stirred solution of 2-(2-(2-(2-((4-(4-((benzyloxy)carbonyl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A5) (74 mg, 0.13 mmol) in dry THF (5 mL) and dry DMF (2 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (65 mg, 0.67 mmol) was added and stirring was continued at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (65 mL) and saturated NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organic layers 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 purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A6 as brown oil (70 mg, 95%); 1H-NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.64 (s, 1H), 7.48 (d, J=8.9 Hz, 2H), 7.37 (d, J=4.3 Hz, 4H), 7.32 (m, 1H), 7.25-7.17 (m, 4H), 6.91 (d, J=9.0 Hz, 2H), 6.51 (d, J=4.9 Hz, 1H), 5.77 (s, 1H), 5.51 (s, 1H), 5.16 (s, 2H), 3.69-3.64 (m, 4H), 3.64 (s, 2H), 3.11-3.06 (m, 4H), 3.05 (dd, J=9.6, 6.5 Hz, 2H), 2.91-2.84 (m, peak obscured), 2.07 (t, J=7.0 Hz 1H). LCMS-A: rt 5.646 min; m/z 551.2 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (65 mL) and saturated NaHCO3 (65 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  4. washthe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas removed in vacuo
  8. customto afford a pale yellow solid which
  9. customwas purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-f2b817a27098445ab4cafdbc7f3f721f
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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