4-Methylmorpholine → HCID 20740224, compound

HRID 1883145Notes

Reaction equation

HRID 1883145 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([NH:13][C@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[C:20](O)=[O:21])=[O:12].CCN=C=NCCCN(C)C.C1[CH:35]=[CH:36][C:37]2[N:42](O)N=[N:40][C:38]=2C=1.C[N:45]1[CH2:50][CH2:49]O[CH2:47][CH2:46]1>O.CN(C=O)C>[C:38]([CH:37]([NH:42][C:20]([C@@H:15]1[CH2:16][CH2:17][CH2:18][CH2:19][C@@H:14]1[NH:13][C:11]([C:3]1[N:2]([CH3:1])[C:10]2[C:5]([CH:4]=1)=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:12])=[O:21])[CH2:36][C:35]1[CH:47]=[CH:46][N:45]=[CH:50][CH:49]=1)#[N:40]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11312620HCID 11312620, compound

Product 1

HCID 20740224HCID 20740224, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To (1R,2S)-2-[(1-methyl-1H-indole-2-carbonyl)-amino]-cyclohexanecarboxylic acid from Example 3 (200 mg, 0.67 mmol) was added EDCI (150 mg, 0.78 mmol), HOBT (110 mg, 0.82 mmol), anhydrous DMF (4 mL), N-methylmorpholine (0.15 mL, 1.3 mmol), and 4-pyridylglycine nitrile hydrochloride salt (4) (160 mg, 1.0 mmol). The reaction mixture was stirred at room temperature for 20 hrs, then 50 mL of water was added and extracted with three 50 mL portions of ethyl acetate. The combined organic layers was washed with three 50 ml portions of water and three 50 mL portions of saturated NaHCO3, dried over sodium sulfate, filtered and concentrated to give a crude foam. Purification by column chromatography (5:95 methanol:dichloromethane) gave 1-methyl-1H-indole-2-carboxylic acid {(1S,2R)-2-[(cyano-pyridin-4-ylmethyl-methyl)-carbamoyl]cyclohexyl}-amide ,165 mg, 58%). MS: 430 (M+H+).

Workup

  1. extractionextracted with three 50 mL portions of ethyl acetate
  2. washThe combined organic layers was washed with three 50 ml portions of water and three 50 mL portions of saturated NaHCO3
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude foam
  7. customPurification by column chromatography (5:95 methanol:dichloromethane)

Sources & evidence

ORD record
ord-080d30238823450693842333953c438d
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

Loading…