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

HRID 872336Notes

Reaction equation

HRID 872336 reaction equation
[C:1]([O:5][C:6](=[O:39])[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]([C:26](=[O:31])N(OC)C)[CH:23]=[CH:22][N:21]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:40][Mg]Cl.[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6](=[O:39])[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]([C:26](=[O:31])[CH3:40])[CH:23]=[CH:22][N:21]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86691041(1-{4-[7-(Methoxy-methyl-carbamoyl)-3-phenyl-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl esterHCID 178418332HCID 178418332, compound

Product 1

HCID 66665323{1-[4-(7-Acetyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (1-{4-[7-(methoxy-methyl-carbamoyl)-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-24-0] (250 mg, 0.48 mmol) in THF (10 mL) under an atmosphere of argon at 0° C. was added a 3 M solution of methyl-magnesium chloride in THF (0.4 mL, 1.2 mmol, 2.5 equiv). The resulting was stirred for 1 h at 0° C., then for 5 h at room temperature. The resulting material was added to a saturated aqueous NH4Cl solution (10 mL). The resulting mixture was extracted with EtOAc (3×20 mL). The combined organic phases were dried (Na2SO4 anh) and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1 min., gradient to 75% hexane/25% EtOAc over 1 min., 75% hexane/25% EtOAc for 3 min., gradient to 50% hexane/50% EtOAc over 1 min., 50% hexane/50% EtOAc for 4.5 min, gradient to 25% hexane/75% EtOAc over 2.5 min., gradient to 100% EtOAc over 2 min., 100% EtOAc for 10.6 min.) to give {1-[4-(7-acetyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (151 mg, 66%):

Workup

  1. customat 0° C.
  2. waitfor 5 h at room temperature
  3. extractionThe resulting mixture was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic phases were dried (Na2SO4 anh)
  5. concentrationconcentrated under reduced pressure
  6. customThe remaining material was purified
  7. customMPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1 min., gradient to 75% hexane/25% EtOAc over 1 min., 75% hexane/25% EtOAc for 3 min., gradient to 50% hexane/50% EtOAc over 1 min., 50% hexane/50% EtOAc for 4.5 min, gradient to 25% hexane/75% EtOAc over 2.5 min., gradient to 100% EtOAc over 2 min., 100% EtOAc for 10.6 min.)

Sources & evidence

ORD record
ord-c1bebc75bc6446e7a19a5b0a48874de0
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

Loading…