Citric Acid → HCID 178510422, compound

HRID 536942Notes

Reaction equation

HRID 536942 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].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCOC(C)=O>[C:26]1([C:12]2[CH:13]=[C:14]([C:17]3([CH2:23][OH:24])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[CH:15]=[CH:16][C:11]=2[NH:10][C:8]([C:5]2[NH:6][CH:7]=[C:3]([C:1]#[N:2])[N:4]=2)=[O:9])[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 178510424HCID 178510424, compound

Product 1

HCID 178510422HCID 178510422, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture 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), 20.0 mg, 0.0476 mmol) and triethylamine (Et3N) (7.3 μL, 0.052 mmol) in 1 mL of THF at 0° C. was added ClCO2Et (3.6 mg, 0.038 mmol). The mixture was stirred at RT for 0.5 h and NaBH4 (5.4 mg, 0.14 mmol) was added. After stirring at RT for 16 h, the mixture was treated with 30 mL of EtOAc and 10 ml of 10% citric acid. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with saturated NaHCO3 aqueous solution (10 mL), H2O (10 mL) and brine (10 mL). After drying over Na2SO4 and concentrating in vacuo, the residue was purified by silica gel chromatography (1-2% MeOH/DCM) to afford the title compound (14 mg, 70%) as a white solid. 1H-NMR (1:5 CD3OD/CDCl3; 400 MHz): δ 8.24 (d, 1H, J=8.6 Hz), 7.72 (s, 1H), 7.26 (dd, 1H, J=8.6, 2.3 Hz), 7.14 (d, 1H, J=2.3 Hz), 5.84 (m, 1H), 3.82 (m, 2H), 3.57 (s, 2H), 3.54-3.60 (m, 2H), 2.27 (m, 4H), 2.14 (m, 2H), 1.95 (m, 2H), 1.82 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C23H26N4O3, 407.2 (M+H). found 407.1.

Workup

  1. stirringAfter stirring at RT for 16 h
  2. customThe aqueous layer was separated
  3. extractionextracted with EtOAc (10 mL)
  4. washThe combined organic layers were washed with saturated NaHCO3 aqueous solution (10 mL), H2O (10 mL) and brine (10 mL)
  5. dry with materialAfter drying over Na2SO4
  6. concentrationconcentrating in vacuo
  7. customthe residue was purified by silica gel chromatography (1-2% MeOH/DCM)

Sources & evidence

ORD record
ord-03b414d48ef9425cb9627a0d503fe6dd
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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