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

HRID 872335Notes

Reaction equation

HRID 872335 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[C:25]([C:27](O)=[O:28])[CH:24]=[CH:23][N:22]4[C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+]([O:53][N:54]2N=NC3C=CC=C[C:55]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:70]N(C=O)C>>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[C:25]([C:27](=[O:28])[N:54]([O:53][CH3:70])[CH3:55])[CH:24]=[CH:23][N:22]4[C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:17][CH:18]=2)[CH2:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 2724699PyBOPHCID 666649662-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridine-7-carboxylic acid

Product 1

HCID 86691041(1-{4-[7-(Methoxy-methyl-carbamoyl)-3-phenyl-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl esterYield 76%

Procedure

A mixture of 2-[4-(1-tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridine-7-carboxylic acid [prepared in a manner analogous to that described in Int-20-0] (750 mg, 1.55 mmol), N-methyl-O-methyl-hydroxlyamine HCl salt (227 mg, 2.33 mmol, 1.5 equiv) N,N-diisopropylethylamine (1.6 mL, 9.30 mmol, 6.0 equiv) and PyBOP (1.01 g, 1.94 mmol, 1.25 equiv) in DMF (23 mL) was stirred at room temperature for 24 h. The resulting mixture was added to ice water (25 mL). The resulting mixture was extracted with EtOAc (4×25 mL). The combined organic phases were washed with water (2×50 mL), 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-(methoxy-methyl-carbamoyl)-3-phenyl-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester (679 mg, 76%):

Workup

  1. customprepared in a manner analogous to
  2. extractionThe resulting mixture was extracted with EtOAc (4×25 mL)
  3. washThe combined organic phases were washed with water (2×50 mL)
  4. dry with materialdried (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-02b95d38970243f4a7c157cf823671b4
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

Loading…