Methyl chloroformate → HCID 178510419, compound

HRID 536941Notes

Reaction equation

HRID 536941 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23](O)=[O:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][C:12]=2[C:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=2)=[O:9])[NH:6][CH:7]=1)#[N:2].ClC(OC)=O.CC[N:39](C(C)C)C(C)C.[OH-].[NH4+]>C1COCC1.CCOC(C)=O>[C:23]([C:17]1([C:14]2[CH:15]=[CH:16][C:11]([NH:10][C:8]([C:5]3[NH:6][CH:7]=[C:3]([C:1]#[N:2])[N:4]=3)=[O:9])=[C:12]([C:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=3)[CH:13]=2)[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1)(=[O:24])[NH2:39]

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 178510424HCID 178510424, compound

Product 1

HCID 178510419HCID 178510419, compoundYield 32.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-{4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-cyclohex-1-enyl-phenyl}-tetrahydro-pyran-4-carboxylic acid (as prepared in Example 18, step (d), 14.5 mg, 0.0345 mmol) in 1 mL of THF was added ClCO2Me (3.6 mg, 0.038 mmol). The mixture was cooled to 0° C., DIEA (18 μL, 0.10 mmol) was added. After warming to RT and stirring for 1 h, the mixture was cooled back to 0° C. Concentrated ammonium hydroxide (25 μL, 0.37 mmol) was added and the resulting mixture was warmed to RT and stirred for 16 h. The reaction was treated with 30 mL of EtOAc and washed with brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (1-5 MeOH/DCM) to afford the title compound (4.7 mg, 32%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 12.00 (s, 1H), 9.53 (s, 1H), 8.33 (d, 1H, J=8.6 Hz), 7.74 (d, 1H, J=2.3 Hz), 7.33 (dd, 1H, J=8.6, 2.3 Hz), 7.20 (d, 1H, J=2.3 Hz), 5.85 (m, 1H), 5.81 (br s, 1H), 5.32 (br s, 1H), 3.82 (m, 4H), 2.38 (m, 2H), 2.19-2.34 (m, 4H), 2.11 (m, 2H), 1.82 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C23H25N5O3, 420.2 (M+H). found 420.1.

Workup

  1. temperatureAfter warming to RT
  2. temperaturethe mixture was cooled back to 0° C
  3. temperaturethe resulting mixture was warmed to RT
  4. stirringstirred for 16 h
  5. washwashed with brine (10 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (1-5 MeOH/DCM)

Sources & evidence

ORD record
ord-46b755f977b343df9a278fe3b472739c
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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