Carbon tetrabromide → HCID 89625010, compound

HRID 1507732Notes

Reaction equation

HRID 1507732 reaction equation
BrC(Br)(Br)Br.CCN([CH:12]([CH3:14])C)C(C)C.[CH3:15][N:16]([CH3:39])[C:17]([C:19]1[N:23]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:22]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[C:21]([OH:37])[C:20]=1[OH:38])=[O:18].[P:40]([O-:47])([O:44][CH2:45][CH3:46])[O:41][CH2:42][CH3:43]>CN(C1C=CN=CC=1)C.CC#N>[CH2:42]([O:41][P:40]([O:37][C:21]1[C:20]([O:38][P:40]([O:47][CH2:12][CH3:14])([O:41][CH2:42][CH3:43])=[O:44])=[C:19]([C:17](=[O:18])[N:16]([CH3:15])[CH3:39])[N:23]([C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[C:22]=1[C:32]([O:34][CH2:35][CH3:36])=[O:33])([O:44][CH2:45][CH3:46])=[O:47])[CH3:43]

Participants

7

Reactant 4

HCID 11205Carbon tetrabromideHCID 81531DiisopropylethylamineHCID 3780918DiethylphosphiteHCID 71576576HCID 71576576, compound

Product 1

HCID 89625010HCID 89625010, compoundYield 22.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

Perbromomethane (207 mg, 0.62 mmol) and DIPEA (131 μL, 0.75 mmol) were added successively to a solution of DMAP (3.05 mg, 0.03 mmol) and ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (UL1-012) (87 mg, 0.25 mmol) in MeCN (3 mL) at −10° C. The reaction mixture was allowed to stir for 30 min and diethyl phosphite (166 μL, 0.75 mmol) added, the reaction was allowed to warm slowly to RT and stirred for 3 h. The reaction was quenched with 5% NaH2PO4 (aq.) (20 mL) and extracted with EtOAc (3×25 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (40 g, 0-4% MeOH in DCM) to afford an orange oil. The compound was further purified by preparative HPLC (C-18 column, 21.2 mm i.d.×100 mm, 5 micron particle size, gradient 5-95% MeCN in 0.1% aq. formic acid over 16 min) to afford ethyl 3,4-bis((diethoxyphosphoryl)oxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (UL1-092) (35 mg, 22%) as a yellow oil: m/z 621 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 7.18-7.15 (m, 2H), 6.97-6.94 (m, 2H), 4.22-4.02 (m, 10H), 3.79 (s, 3H), 2.75 (s, 3H), 2.71 (s, 3H), 1.31-1.24 (m, 12H),1.07 (t, J=7.2 Hz, 3H).

Workup

  1. stirringstirred for 3 h
  2. customThe reaction was quenched with 5% NaH2PO4 (aq.) (20 mL)
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe combined organics were washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by silica gel chromatography (40 g, 0-4% MeOH in DCM)
  9. customto afford an orange oil
  10. customThe compound was further purified by preparative HPLC (C-18 column, 21.2 mm i.d.×100 mm, 5 micron particle size, gradient 5-95% MeCN in 0.1% aq. formic acid over 16 min)

Sources & evidence

ORD record
ord-788eeb43fe2647fd9fa91ef4717cd5ed
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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