Pyridine → [4-(3-cyano-1-cyclobutyl-6-(2-methoxyethoxy)-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester

HRID 502250Notes

Reaction equation

HRID 502250 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:24]3[CH2:27][CH2:26][CH2:25]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:11]=3)=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:35]([O:37][C:38]1[CH:43]=[CH:42][C:41]([N+]([O-])=O)=C[CH:39]=1)=[O:36].CC(C1CC1)O>ClC(Cl)C>[CH:43]1([CH:38]([O:37][C:35](=[O:36])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:9]([CH:24]4[CH2:27][CH2:26][CH2:25]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:11]=4)=[CH:6][CH:7]=2)[CH3:39])[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 791041-CyclopropylethanolHCID 821294-Nitrophenyl chloroformateHCID 594253792-(4-aminophenyl)-1-cyclobutyl-6-(2-methoxyethoxy)-1H-indole-3-carbonitrile

Product 1

HCID 59425128[4-(3-cyano-1-cyclobutyl-6-(2-methoxyethoxy)-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 2-(4-aminophenyl)-1-cyclobutyl-6-(2-methoxy-ethoxy)-1H-indole-3-carbonitrile (76.0 mg, 0.21 mmol), pyridine (36.5 mg, 0.46 mmol) in 10 mL of 1,1 dichloroethane is added 4-nitrophenyl chloroformate (93.2 mg, 0.46 mmol). The resulting mixture is stirred at room temperature for 2 h. Then α-methylcyclopropane methanol (54.3 mg, 0.63 mmol) is added. The reaction mixture is heated to 70° C. for 5 h. After cooling, the reaction is partitioned between ethyl acetate (10 mL) and saturated K2CO3 (10 mL). The organic phase is washed with additional saturated K2CO3 (2×10 mL), water, and saturated NaCl. The colorless solution is dried over MgSO4, filtered and evaporated. The remaining solid is washed with diethyl ether to yield the title compound, of [4-(3-cyano-1-cyclobutyl-6-(2-methoxyethoxy)-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester (compound 1423) as a white solid.

Workup

  1. temperatureThe reaction mixture is heated to 70° C. for 5 h
  2. temperatureAfter cooling
  3. customthe reaction is partitioned between ethyl acetate (10 mL) and saturated K2CO3 (10 mL)
  4. washThe organic phase is washed with additional saturated K2CO3 (2×10 mL), water, and saturated NaCl
  5. dry with materialThe colorless solution is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. washThe remaining solid is washed with diethyl ether

Sources & evidence

ORD record
ord-e6f2181a6c1e4db5979b372932723f4f
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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