1,3-Dibromopropane → HCID 58431207, compound

HRID 1040571Notes

Reaction equation

HRID 1040571 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]2([NH:14][C:15]([C:17]3([NH:20][C:21]([C:23]4[N:27]5[C@@:28]([CH2:41][C:42]6[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=6)([CH3:40])[C:29](=[O:39])[N:30]([C:31]6[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=6)[C:26]5=[N:25][CH:24]=4)=[O:22])[CH2:19][CH2:18]3)=[O:16])[CH2:13][CH2:12]2)[CH:6]=1.CCN(C(C)C)[CH:53]([CH3:55])[CH3:54].BrCCCBr>CC(N(C)C)=O.CCOC(C)=O>[N:3]1([CH2:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([C:11]3([NH:14][C:15]([C:17]4([NH:20][C:21]([C:23]5[N:27]6[C@@:28]([CH2:41][C:42]7[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=7)([CH3:40])[C:29](=[O:39])[N:30]([C:31]7[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=7)[C:26]6=[N:25][CH:24]=5)=[O:22])[CH2:18][CH2:19]4)=[O:16])[CH2:12][CH2:13]3)[CH:6]=2)[CH2:55][CH2:53][CH2:54]1

Participants

6

Reactant 3

HCID 80011,3-DibromopropaneHCID 81531DiisopropylethylamineHCID 86657596HCID 86657596, compound

Product 1

HCID 58431207HCID 58431207, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To the solution of (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid {1-[1-(4-aminomethyl-pyridin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-amide dihydrochloric acid salt (60 mg, 0.081 mmol) in dry DMA (5 mL) was added DIPEA (0.071 mL, 0.405 mmol) followed by 1,3-dibromopropane (0.0415 mL, 0.405 mmol). The reaction mixture was heated in the microwave at 100° C. for 2×10 min. Diluted with EtOAc (50 mL). Washed with saturated NaHCO3 (2×25 mL). Layers were separated. The organic layer was dried, filtered, and concentrated. The resultant crude product was purified by prep-TLC using 5% MeOH/DCM as the eluent. The prep TLC plate looked messy, presumably due to the significant existence of DMA. The product fraction was collected and redissolved in EtOAc (50 mL), washed with water (3×15 mL), dried, filtered, and concentrated. The crude product was purified by prep-TLC using 5% MeOH/DCM as the eluent to afford 7.5 mg of the title compound as a light yellow solid, m/z 709.8 [M+1]+.

Workup

  1. washWashed with saturated NaHCO3 (2×25 mL)
  2. customLayers were separated
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resultant crude product was purified
  7. customThe product fraction was collected
  8. dissolutionredissolved in EtOAc (50 mL)
  9. washwashed with water (3×15 mL)
  10. customdried
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified

Sources & evidence

ORD record
ord-d40b3157ae2c40468a08a27abf278f46
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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