Hydrochloric Acid → 5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)nicotinamide

HRID 924127Notes

Reaction equation

HRID 924127 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[NH:23]1[CH2:27][C@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]1.CCN(C(C)C)C(C)C.Cl>CC(O)C.C1CCCCC1.CCOC(C)=O>[Br:1][C:2]1[C:3]([N:23]2[CH2:27][C@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1461981,4-Dideoxy-1,4-iminothreitolHCID 725460895-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 899065275-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)nicotinamide

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 21867204Cyclohexane ethylacetateSolvent

Procedure

A suspension of 5-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide (Stage 169.2, 1 g, 2.427 mmol) and (3S,4S)-pyrrolidine-3,4-diol (0.3 g, 2.91 mmol) in a mixture of DIPEA (1.272 mL, 7.28 mmol) and iPrOH (3.24 mL) was subjected to MW irradiation at 140° C. for 1 h. The RM was treated with 0.5 M HCl (40 mL) and extracted with EtOAc. The combined extracts were washed with water, sat. aq. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue that was suspended in a mixture of cyclohexane EtOAc. The resulting solid was filtered-off, washed with cyclohexane and dried to afford the title product as an off-white solid. UPLC-MS (Condition 3) tR=0.98 min, m/z=477.9 [M+H]+, m/z=475.8 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.55 (d, J=11.13 Hz, 2H) 3.91-4.09 (m, 4H) 5.18 (d, J=2.81 Hz, 2H) 7.34 (d, J=9.05 Hz, 2H) 7.80-7.93 (m, 2H) 8.34 (d, J=1.96 Hz, 1H) 8.67 (d, J=1.96 Hz, 1H) 10.24 (s, 1H).

Workup

  1. customwas subjected to MW irradiation at 140° C. for 1 h
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with water, sat. aq. NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue that
  7. washwashed with cyclohexane
  8. customdried

Sources & evidence

ORD record
ord-2cf72f49c2b54ed89d99b28bec7e1e7e
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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