Ammonium Chloride → HCID 89610373, compound

HRID 1507717Notes

Reaction equation

HRID 1507717 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([O:32][C:33]1[C:34]([O:56][CH2:57][C:58](O)=[O:59])=[C:35]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[N:36]([C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[C:37]=1[C:38]([O:40][CH2:41][CH3:42])=[O:39])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.[NH4+:70].[Cl-]>C1COCC1>[NH2:70][C:58](=[O:59])[CH2:57][O:56][C:34]1[C:33]([O:32][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[N:36]([C:43]2[CH:44]=[CH:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=2)[C:35]=1[C:51]([O:53][CH2:54][CH3:55])=[O:52]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89610490HCID 89610490, compound

Product 1

HCID 89610373HCID 89610373, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

HATU (153 mg, 0.40 mmol) was added to a stirred solution 2-((4-(benzyloxy)-2,5-bis(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrol-3-yl)oxy)acetic acid (24) (100 mg, 0.20 mmol), DIPEA (176 μL, 1.00 mmol), and NH4Cl (53.8 mg, 1.00 mmol) in THF (2 mL) at 0° C. The reaction mixture was stirred at 0° C. for 20 min and then at RT for 2 h volatiles were removed in vacuo, dissolved in EtOAc (30 mL) and washed with 1 M HCl (3×30 mL), sat. NaHCO3 (aq.) (3×30 mL) and brine (30 mL), dried (MgSO4), filtered and solvents removed in vacuo to give a yellow oil. The product was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane) to afford diethyl 3-(2-amino-2-oxoethoxy)-4-(benzyloxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate (25) (66 mg, 66%) as a white solid: m/z 497 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 7.58 (br s, 1H), 7.51 (br s, 1H), 7.49-7.44 (m, 2H), 7.43-7.33 (m, 3H), 7.17-7.09 (m, 2H), 6.95-6.86 (m, 2H), 5.10 (s, 2H), 4.46 (s, 2H), 4.00 (q, J=7.1 Hz, 2H), 3.98 (q, J=7.1 Hz, 2H), 3.79 (s, 3H), 0.97 (t, J=7.1 Hz, 3H), 0.96 (t, J=7.1 Hz, 3H).

Workup

  1. customat RT for 2 h volatiles were removed in vacuo
  2. dissolutiondissolved in EtOAc (30 mL)
  3. washwashed with 1 M HCl (3×30 mL), sat. NaHCO3 (aq.) (3×30 mL) and brine (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customsolvents removed in vacuo
  7. customto give a yellow oil
  8. customThe product was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-6a9da379dc5145af80f2f140cb59c3db
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

Loading…