Hydrochloric Acid → HCID 73055749, compound

HRID 1779085Notes

Reaction equation

HRID 1779085 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.[CH3:33][C:34]1[C:35]([CH2:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[CH2:55][C:56]([OH:58])=O)=[N:36][C:37]([NH:40][C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)=[N:38][CH:39]=1.C(=O)([O-])[O-].[NH4+].[NH4+]>CN(C=O)C>[CH3:33][C:34]1[C:35]([CH2:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[CH2:55][C:56]([NH2:7])=[O:58])=[N:36][C:37]([NH:40][C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)=[N:38][CH:39]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712722HCID 86712722, compound

Product 1

HCID 73055749HCID 73055749, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HOBt (0.074 g, 0.55 mmol), EDCl.HCl (0.117 g, 0.610 mmol) and DIPEA (0.16 mL, 0.94 mmol) were added to a solution of 2-(2-(2-(5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A117) (0.066 g, 0.19 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (0.180 g, 1.88 mmol) was added in one portion and the resulting mixture stirred for 18 hours at room temperature. The volatiles were removed in vacuo and the residue partitioned between EtOAc (50 mL) and aqueous saturated 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 and the residue purified by silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-30% MeOH in EtOAc) to give the title compound 28 as a yellow solid (0.040 g, 61%); 1H NMR (400 MHz, d6-DMSO) δ 9.18 (s, 1H), 8.10 (s, 1H), 7.86 (s, 1H), 7.43 (s, 2H), 7.28-7.10 (m, 4H), 6.93 (s, 1H), 3.78 (s, 3H), 3.49 (s, 2H), 3.07-2.98 (m, 2H), 2.90-2.81 (m, 2H), 2.04 (s, 3H). LCMS-A: rt 4.464 min; m/z 351 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (50 mL) and aqueous saturated NaHCO3 (50 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×25 mL)
  4. washThe combined organic layers were washed with brine (25 mL)
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e719eaaab58e4780b3647bcc2888b101
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

Loading…