Water → {1-[4-(7-Acetylamino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872333Notes

Reaction equation

HRID 872333 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([NH2:26])[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:35](OC(=O)C)(=[O:37])[CH3:36].N1C=CC=CC=1.O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([NH:26][C:35](=[O:37])[CH3:36])[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 66665799{1-[4-(7-Amino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665742{1-[4-(7-Acetylamino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of {1-[4-(7-amino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [prepared in a manner analogous to that described in Int-21-0] (225 mg, 0.50 mmol), acetic anhydride (0.061 mL, 6.4 mmol, 1.3 equiv) and pyridine (0.10 mL, 1.24 mmol, 2.5 equiv) in CH2Cl2 (7 mL) was stirred at room temperature for 48 h. The resulting mixture was added to water (10 mL). The resulting mixture was extracted with CH2Cl2 (3×10 mL). The combined organic phases were dried (Na2SO4 anh) and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 100% CH2Cl2 for 2 min., gradient to 95% CH2Cl2: 5% MeOH over 1 min.; 95% CH2Cl2: 5% MeOH for 4.5 min., gradient to 90% CH2Cl2: 10% MeOH over 4 min., 90% CH2Cl2: 10% MeOH for 3 min., gradient to 80% CH2Cl2: 20% MeOH over 5 min., 80% CH2Cl2: 20% MeOH for 4.8 min.) to give {1-[4-(7-acetylamino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (151 mg, 61%):

Workup

  1. extractionThe resulting mixture was extracted with CH2Cl2 (3×10 mL)
  2. dry with materialThe combined organic phases were dried (Na2SO4 anh)
  3. concentrationconcentrated under reduced pressure
  4. customThe remaining material was purified
  5. wait100% CH2Cl2 for 2 min.
  6. waitgradient to 95% CH2Cl2: 5% MeOH over 1 min.
  7. wait95% CH2Cl2: 5% MeOH for 4.5 min.
  8. waitgradient to 90% CH2Cl2: 10% MeOH over 4 min.
  9. wait90% CH2Cl2: 10% MeOH for 3 min.
  10. waitgradient to 80% CH2Cl2: 20% MeOH over 5 min.

Sources & evidence

ORD record
ord-ff21fc1a78c047468047e97125084e5d
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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