Bromoacetyl bromide → HCID 66937224, compound

HRID 538211Notes

Reaction equation

HRID 538211 reaction equation
C(N(C(C)C)CC)(C)C.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:24]([CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])[C:23]3[CH:31]=[C:32]([Cl:36])[C:33]([NH2:35])=[CH:34][C:22]=3[N:21]=2)[CH:19]=1)=[O:14])[CH3:11].NC1C(Cl)=CC2NC(N3C=C(C(O)=O)C=N3)=NC=2C=1.[Br:56][CH2:57][C:58](Br)=[O:59]>CCOC(C)=O.O.C1COCC1>[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:24]([CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])[C:23]3[CH:31]=[C:32]([Cl:36])[C:33]([NH:35][C:58](=[O:59])[CH2:57][Br:56])=[CH:34][C:22]=3[N:21]=2)[CH:19]=1)=[O:14])[CH3:11]

Participants

8

Reactant 4

HCID 61147Bromoacetyl bromide2×HCID 81531DiisopropylethylamineHCID 444790641-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acidHCID 669373191-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 66937224HCID 66937224, compoundYield 42.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of diisopropylethylamine (0.86 mL, 4.95 mmol), 1-[5-amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate from Example 41, product from Step A) (0.650 g, 1.65 mmol), and THF (8 mL) at 0° C., was added bromoacetyl bromide (0.244 mL, 2.81 mmol). The reaction mixture was allowed to slowly warm to 23° C. A second aliquot of bromoacetyl bromide (0.244 mL, 2.81 mmol) was added and the reaction mixture was kept at 23° C. for an additional 25 min. Water was added (20 mL) and the aqueous layer was extracted with EtOAc (2×75 mL). The combined organic layers were washed with brine (25 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-45% EtOAc/hexanes) to yield the titled compound (0.361 g, 42% yield) after trituration with EtOAc. A 3:2 mixture of regioisomers was observed in the 1H NMR spectrum. MS (ESI/CI): mass calcd. for C19H21BrClN5O5, 513.0; m/z found, 514.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.89 (s, 1H), 8.87 (br s, 1H), 8.71 (s, 1H), 8.18 (s, 1H), 7.70 (s, 1H), 6.13 (s, 2H), 4.36 (q, J=7.2 Hz, 2H), 4.13 (s, 2H), 3.68-3.62 (m, 2H), 3.49-3.43 (m, 2H), 3.31 (s, 3H), 1.38 (t, J=7.1 Hz, 3H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (2×75 mL)
  2. washThe combined organic layers were washed with brine (25 mL)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified (FCC) (10-45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a7bbb264b84f4d50a246d513c2f88f23
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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