Diisopropylethylamine → tert-Butyl 1-(4-(3-(4-fluorophenylamino)-3-oxopropanamido)phenyl)-1H-pyrrolo[3,2-c]pyridin-4-ylcarbamate

HRID 230744Notes

Reaction equation

HRID 230744 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[CH:14][N:13]=[C:12]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:11]=3[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:38])[CH2:34][C:35](O)=[O:36])=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[F:25][C:26]1[CH:27]=[CH:28][C:29]([NH:32][C:33](=[O:38])[CH2:34][C:35]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C:16]4[CH:15]=[CH:14][N:13]=[C:12]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:23])[CH3:22])[C:11]=4[CH:10]=[CH:9]3)=[CH:4][CH:3]=2)=[O:36])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acidHCID 57763144Tert-butyl 1-(4-aminophenyl)-1h-pyrrolo[3,2-c]pyridin-4-ylcarbamate2×

Product 1

HCID 57763151tert-Butyl 1-(4-(3-(4-fluorophenylamino)-3-oxopropanamido)phenyl)-1H-pyrrolo[3,2-c]pyridin-4-ylcarbamateYield 56,524,596%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl 1-(4-aminophenyl)-1H-pyrrolo[3,2-c]pyridin-4-ylcarbamate (27 mg, 0.083 mmol, Compound B of Example 1) in DMF (1 mL) was treated with 3-(4-fluorophenylamino)-3-oxopropanoic acid (25 mg, 0.13 nmol), DIPEA (21 μL, 0.13 mmol) and TBTU (40 mg, 0.13 mmol) and the mixture stirred at RT for 16 h. The mixture was concentrated in vacuo to remove the DMF and the residue was partitioned between EtOAc (2 mL) and saturated sodium bicarbonate solution (2 mL). The EtOAc phase was washed with 10% aqueous LiCl (2 mL), brine (2 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified using a Chromatotron (1 mm SiO2 GF rotor, 2-5% MeOH-CHCl3 gradient elution) to give the title compound (37 mg, 88%) as an off-white solid. LCMS (ESI+) m/z 504 (M+H)+; HPLC tR=3.49 min.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto remove the DMF
  3. customthe residue was partitioned between EtOAc (2 mL) and saturated sodium bicarbonate solution (2 mL)
  4. washThe EtOAc phase was washed with 10% aqueous LiCl (2 mL), brine (2 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified
  8. washa Chromatotron (1 mm SiO2 GF rotor, 2-5% MeOH-CHCl3 gradient elution)

Sources & evidence

ORD record
ord-afb498b2ff5a4ae1b44417f73cea8223
Source dataset
uspto-grants-2009_07
Patent number
US07566784B2

Reaction notes

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