Hydrochloric Acid → HCID 73055447, compound

HRID 1779066Notes

Reaction equation

HRID 1779066 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(OC([N:40]1[CH2:45][CH2:44][CH: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]([O:71][CH3:72])=[CH:55][N:54]=3)=[CH:48][CH:47]=2)[CH2:42][CH2:41]1)=O)(C)(C)C.C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[CH3:72][O:71][C:56]1[C:57]([CH2:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=2[CH2:67][C:68]([NH2:7])=[O:70])=[N:58][C:53]([NH:52][C:49]2[CH:50]=[CH:51][C:46]([CH:43]3[CH2:42][CH2:41][NH:40][CH2:45][CH2:44]3)=[CH:47][CH:48]=2)=[N:54][CH:55]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712708HCID 86712708, compound

Product 1

HCID 73055447HCID 73055447, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

HOBt (0.032 g, 0.24 mmol), EDCl.HCl (0.045 g, 0.24 mmol) and DIPEA (0.16 mL, 0.91 mmol) were added to a solution of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-methoxypyrimidin-4-yl)ethyl)phenyl)acetic acid (A101) (0.099 g, 0.18 mmol) in dry THF (6 mL) and dry DMF (1 mL) under nitrogen. After 10 minutes ammonium carbonate (0.087 g, 0.91 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 66 hours. The volatiles were removed in vacuo and the residue partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL) and dried over MgSO4. 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 0-20% MeOH in EtOAc) to give the title compound A102 as a clear oil (0.094 g, 92%); 1H NMR (400 MHz, d4-MeOH) δ 8.00 (s, 1H), 7.53 (d, J=8.6 Hz, 2H), 7.22 (dd, J=7.0, 3.8 Hz, 1H), 7.20-7.13 (m, 3H), 7.10 (d, J=8.6 Hz, 2H), 4.18 (d, J=13.0 Hz, 2H), 3.78 (s, 3H), 3.65 (s, 2H), 3.10-3.00 (m, 2H), 3.00-2.92 (m, peak obscured, 2H), 2.90-2.71 (m, peak obscured, 2H), 2.62 (tt, J=11.9, 3.2 Hz, 1H), 1.78 (d, J=12.2 Hz, 2H), 1.60-1.49 (m, 2H), 1.47 (s, 9H). LCMS-A: rt 6.20 min; m/z 546.4 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 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 MgSO4
  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 0-20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-ea101ce101214e138ec94ac7d86656b1
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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