Ethyl Acetate → {6-(2,4-Dichloro-phenyl)-3-[(tetrahydro-pyran-4-carbonyl)-amino]-imidazo[1,2-a]pyridin-7-ylmethyl}-carbamic acid tert-butyl ester

HRID 420534Notes

Reaction equation

HRID 420534 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:23]([NH2:26])=[CH:24][N:25]=[C:11]2[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].CCN([CH:34]([CH3:36])[CH3:35])C(C)C.CN([C:40]([O:44]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCO[C:64]([CH3:66])=[O:65]>CN(C=O)C>[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:23]([NH:26][C:40]([CH:35]3[CH2:34][CH2:36][O:65][CH2:64][CH2:66]3)=[O:44])=[CH:24][N:25]=[C:11]2[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57906484[3-Amino-6-(2,4-dichloro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl]-carbamic acid tert-butyl ester

Product 1

HCID 57906481{6-(2,4-Dichloro-phenyl)-3-[(tetrahydro-pyran-4-carbonyl)-amino]-imidazo[1,2-a]pyridin-7-ylmethyl}-carbamic acid tert-butyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of [3-amino-6-(2,4-dichloro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl]-carbamic acid tert-butyl ester (100 mg, 0.25 mmol), tetrahydro-pyran-4-arboxylic acid (192 mg, 1.47 mmol) and DIPEA (0.52 mL, 2.95 mmol) in DMF (3 mL) was added HATU (560 mg, 1.47 mmol) at RT. The reaction mixture was heated at 80° C. and stirred for 24 h, then poured into AcOEt (50 mL) and washed with a 2.0 M aqueous Na2CO3 solution (2×25 mL). The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH 99:1→84:16) to yield the title compound (79.5 mg, 0.153 mmol, 62%). MS: 519 [M+1]+; HPLC: AtRet=1.49; TLC: RF 0.14 (DCM/MeOH 95:5).

Workup

  1. washwashed with a 2.0 M aqueous Na2CO3 solution (2×25 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH 99:1→84:16)

Sources & evidence

ORD record
ord-59377f9632604eceaaf9b36c8a2b60da
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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