Ethanolamine → HCID 178457953, compound

HRID 1508023Notes

Reaction equation

HRID 1508023 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.C(O)(=O)C.[NH2:17][C:18]([C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28]([C:30]2[NH:31][CH:32]=[C:33]([C:35]#[N:36])[N:34]=2)=[O:29])=[C:23]([C:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]=2)[CH:22]=1)([CH3:20])[CH3:19].CCN(C(C)C)C(C)C.[NH2:52][CH2:53][CH2:54][OH:55]>C1COCC1.[Cl-].[Na+].O>[C:37]1([C:23]2[CH:22]=[C:21]([C:18]([NH:17][C:2]([NH:52][CH2:53][CH2:54][OH:55])=[O:4])([CH3:20])[CH3:19])[CH:26]=[CH:25][C:24]=2[NH:27][C:28]([C:30]2[NH:31][CH:32]=[C:33]([C:35]#[N:36])[N:34]=2)=[O:29])[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178476304HCID 178476304, compound

Product 1

HCID 178457953HCID 178457953, compoundYield 86.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of triphosgene (11.9 mg, 0.0400 mmol) in 2 mL of THF at 0° C. was added a solution of 4-cyano-1H-imidazole-2-carboxylic acid [4-(1-amino-1-methyl-ethyl)-2-cyclohex-1-enyl-phenyl]-amide acetic acid salt (as prepared in Example 3, step (b), 41.0 mg, 0.100 mmol) and DIEA (52 μL, 0.30 mmol) in 2 mL of THF under Ar. The resulting mixture was stirred at RT for 10 min and cooled to 0° C. 2-Amino-ethanol (60.0 μL, 1.00 mmol) was added into the mixture and the reaction was stirred at RT for 2 h. The mixture was treated with brine (10 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were concentrated in vacuo and the residue was purified by flash chromatography on silica gel (2-8% MeOH/DCM) to give 15.1 mg (35%) of the title compound as a light yellow oil. 1H-NMR (CD3OD; 400 MHz): δ 8.11 (d, 1H, J=8.4 Hz), 7.99 (s, 1H), 7.31 (dd, 1H, J=8.4, 2.4 Hz), 7.21 (d, 1H, J=2.4 Hz), 6.48 (s, 1H), 5.80 (m, 1H), 3.52 (t, 2H, J=5.6 Hz), 3.16 (t, 2H, J=5.6 Hz), 2.20-2.33 (m, 4H), 1.73-1.88 (m, 4H), 1.60 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C23H28N6O3, 437.2 (M+H). found 437.1.

Workup

  1. temperaturecooled to 0° C
  2. stirringthe reaction was stirred at RT for 2 h
  3. extractionextracted with EtOAc (2×25 mL)
  4. concentrationThe combined organic layers were concentrated in vacuo
  5. customthe residue was purified by flash chromatography on silica gel (2-8% MeOH/DCM)

Sources & evidence

ORD record
ord-5126821f45594d5281ea793080f4c9cb
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

Loading…