Hydrochloric Acid → HCID 86712645, compound

HRID 1778976Notes

Reaction equation

HRID 1778976 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]([C:46]2[N: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:48]=[CH:47][C:46]([CH:43]3[CH2:42][CH2:41][N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:39])[CH2:45][CH2:44]3)=[N:51][CH:50]=2)[N:58]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712644HCID 86712644, compound

Product 1

HCID 86712645HCID 86712645, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HOBt (71 mg, 0.52 mmol), EDCl.HCl (0.11 g, 0.59 mmol) and DIPEA (0.16 mL, 0.90 mmol) were added to a stirred solution of 2-(2-(2-(2-((6-(1-(tert-butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-methylpyrimidin-4-ylethyl)phenyl)acetic acid (A19) (96 mg, 0.18 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (174 mg, 1.81 mmol) was added in one portion and the resulting mixture was stirred for 18 hours at room temperature. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) then the combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The volatiles were removed in vacuo and the residue adsorbed onto silica gel and purified by chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in DCM) to give the title compound A20 as a clear oil (72 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J=2.4 Hz, 1H), 8.14-8.06 (m, 1H), 7.93 (dd, J=8.5, 2.7 Hz, 1H), 7.37 (s, 1H), 7.26-7.22 (m, 4H), 7.10 (d, J=8.5 Hz, 1H), 5.91 (s, 1H), 5.73 (s, 1H), 4.24 (s, 2H), 3.69 (s, 2H), 3.09 (dd, J=9.7, 6.0 Hz, 2H), 2.97-2.90 (m, 2H), 2.86-2.72 (m, 3H), 2.12 (s, 3H), 1.90 (d, J=12.8 Hz, 2H), 1.68 (m, 2H), 1.47 (s, 9H). LCMS-A: rt 5.018 min; m/z 531 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. customThe volatiles were removed in vacuo
  7. custompurified by chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in DCM)

Sources & evidence

ORD record
ord-e7ac6a3349a2469dad96dcce835b6454
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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