Diisopropylethylamine → HCID 178457612, compound

HRID 1508022Notes

Reaction equation

HRID 1508022 reaction equation
ClC(Cl)(O[C:5](=[O:11])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].CC[N:45](C(C)C)C(C)C>C1COCC1>[C:37]1([C:23]2[CH:22]=[C:21]([C:18]([CH3:20])([NH:17][C:5]([NH2:45])=[O:11])[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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178476304HCID 178476304, compound

Product 1

HCID 178457612HCID 178457612, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of triphosgene (7.2 mg, 0.024 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), 25.0 mg, 0.0611 mmol) and DIEA (32 μL, 0.18 mmol) in 2 mL of THF under Ar. The resulting mixture was stirred at RT for 20 min and cooled to 0° C. NH3 (g) was bubbled into the mixture for ca. 4 min and the reaction was then sealed and stirred at RT for 0.5 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 (3-6% MeOH/DCM) to afford 7.2 mg (30%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.11 (d, 1H, J=8.6 Hz), 7.98 (s, 1H), 7.32 (dd, 1H, J=8.6, 2.1 Hz), 7.22 (d, 1H, J=2.1 Hz), 5.80 (m, 1H), 2.20-2.34 (m, 4H), 1.73-1.89 (m, 4H), 1.61 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C21H24N6O2, 393.2 (M+H). found 393.0.

Workup

  1. temperaturecooled to 0° C
  2. customNH3 (g) was bubbled into the mixture for ca. 4 min
  3. customthe reaction was then sealed
  4. stirringstirred at RT for 0.5 h
  5. additionThe mixture was treated with brine (10 mL)
  6. extractionextracted with EtOAc (2×25 mL)
  7. concentrationThe combined organic layers were concentrated in vacuo
  8. customthe residue was purified by flash chromatography on silica gel (3-6% MeOH/DCM)

Sources & evidence

ORD record
ord-73b1fc2d991f4ad5ad7d05a677b9c7ee
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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