N-bromobutanimide → HCID 53353198, compound

HRID 2405107Notes

Reaction equation

HRID 2405107 reaction equation
[CH:1]1([N:4]2[C:12]3[CH:11]=[C:10]([NH:13][C:14](=[O:26])[C:15]4[CH:20]=[CH:19][C:18]([C@:21]([OH:25])([CH3:24])[CH2:22][OH:23])=[CH:17][CH:16]=4)[N:9]=[CH:8][C:7]=3[CH:6]=[CH:5]2)[CH2:3][CH2:2]1.[Br:27]N1C(=O)CCC1=O>CN(C)C=O.[Cl-].[Na+].O>[Br:27][C:6]1[C:7]2[CH:8]=[N:9][C:10]([NH:13][C:14](=[O:26])[C:15]3[CH:20]=[CH:19][C:18]([C@:21]([OH:25])([CH3:24])[CH2:22][OH:23])=[CH:17][CH:16]=3)=[CH:11][C:12]=2[N:4]([CH:1]2[CH2:3][CH2:2]2)[CH:5]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimide2×HCID 53354694HCID 53354694, compound

Product 1

HCID 53353198HCID 53353198, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In a 250 ml round bottom flask was added (R)—N-(1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (17, 3.2 g, 9.2 mmol) in N,N-dimethylformamide (31 ml). The mixture was cooled in ice bath, followed by addition of N-bromosuccinimide (1.477 g, 8.30 mmol) in portions. The mixture was stirred in ice bath for 30 min, at which point about ˜10% starting material remained. Another 0.1 equivalence (160 mg) of N-bromosuccinimide was added to the reaction mixture, which was stirred in an ice bath for another 30 min. Brine (200 ml) was added, followed by extraction with EtOAc (2×200 mL). Organic layers were combined. After drying and filtering, a suspension was obtained upon concentration. The solid was collected on a filtered, and then washed with 10 ml EtOAc. The resulting 2 g of filtrated solid was purified by silica gel column chromatography, eluting with 5-10% MeOH in EtOAc. Product-containing fractions were combined and concentrated to yield a solid which was washed twice with EtOAc (2×10 ml). The title compound (22, 0.62 g, 16%) was obtained as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98-1.04 (m, 2H) 1.05-1.13 (m, 2H) 1.42 (s, 3H) 3.42-3.54 (m, 3 H) 4.71 (t, J=5.81 Hz, 1H) 4.99 (s, 1H) 7.58 (d, J=8.59 Hz, 2H) 7.62 (s, 1H) 8.01 (d, J=8.59 Hz, 2H) 8.48 (d, J=0.76 Hz, 2H) 8.51 (d, J=0.76 Hz, 2H) 10.63 (s, 1H); ESI-MS: m/z 432 (M+H)+. Additional amounts of the title compound were obtained by combining filtrates and re-purifying them by silica gel column chromatography.

Workup

  1. temperatureThe mixture was cooled in ice bath
  2. stirringwas stirred in an ice bath for another 30 min
  3. extractionfollowed by extraction with EtOAc (2×200 mL)
  4. customAfter drying
  5. filtrationfiltering
  6. customa suspension was obtained upon concentration
  7. customThe solid was collected on a filtered
  8. washwashed with 10 ml EtOAc
  9. customThe resulting 2 g of filtrated solid was purified by silica gel column chromatography
  10. washeluting with 5-10% MeOH in EtOAc
  11. concentrationconcentrated
  12. customto yield a solid which
  13. washwas washed twice with EtOAc (2×10 ml)

Sources & evidence

ORD record
ord-fac2ecaeb0c04ca6b114aa8bccb4eb3a
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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