Ethyl Acetate → HCID 58081300, compound

HRID 928452Notes

Reaction equation

HRID 928452 reaction equation
CN1C2=N[CH:8]=[C:9]([CH2:11][N:12]3[CH:16]=[C:15]([C:17](O)=[O:18])[CH:14]=[N:13]3)[CH:10]=C2C=C1.[NH2:20][CH2:21][C:22]1[C:23]([CH3:37])=[CH:24][C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[N:26][C:27]=1[CH3:28].C[CH2:39][N:40]([CH:44]([CH3:46])[CH3:45])[CH:41]([CH3:43])[CH3:42].CC(=O)OCC>C(Cl)Cl>[CH3:39][N:40]1[C:44]2[C:46](=[CH:10][C:9]([CH2:11][N:12]3[CH:16]=[C:15]([C:17]([NH:20][CH2:21][C:22]4[C:23]([CH3:37])=[CH:24][C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[N:26][C:27]=4[CH3:28])=[O:18])[CH:14]=[N:13]3)=[CH:8][CH:45]=2)[CH:42]=[C:41]1[CH3:43]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 22475372N-[5-(aminomethyl)-4,6-dimethyl(2-pyridyl)] (tert-butoxy)carboxamideHCID 66723545HCID 66723545, compound

Product 1

HCID 58081300HCID 58081300, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((1-Methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl)-1H-pyrazole-4-carboxylic acid (130 mg, 0.330 mmol, 65%), tert-Butyl 5-(aminomethyl)-4,6-dimethylpyridin-2-ylcarbamate (99 mg, 0.396 mmol) and DIPEA (0.308 ml, 1.764 mmol) in DCM (4 ml) Propanephosphonic anhydride (50% in EA (0.156 ml, 0.529 mmol) was added at rt. The reaction mixture was stirred at it for 1 h. The reaction mixture was quenched with 1 N NaOH and extracted twice with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash-chromatography on silica gel (26 g), gradient of DCM/DCM:MeOH 8:2 (40 ml/min.) from 100/0 (5 min.) to 80/20 (20 min.) to 80/20 5 min. to afford tert-Butyl 5-((1-((1,2-dimethyl-1H-indol-5-yl)methyl)-1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-ylcarbamate. MS (Method V) [M+H]+=503.4.

Workup

  1. customThe reaction mixture was quenched with 1 N NaOH
  2. extractionextracted twice with DCM
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by flash-chromatography on silica gel (26 g), gradient of DCM/DCM

Sources & evidence

ORD record
ord-69aedd67e74d4e7b83f51b810b39e275
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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