Water → HCID 44515656, compound

HRID 1923919Notes

Reaction equation

HRID 1923919 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:14]([Br:15])=[CH:13][N:12]=[C:11]3[NH:16][CH:17]=[C:18]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[C:10]=23)[CH2:4]1.Br[CH2:26][CH2:27][O:28][CH3:29].CCN(C(C)C)C(C)C.O>CN(C=O)C>[Br:15][C:14]1[C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([NH:2][CH2:26][CH2:27][O:28][CH3:29])[CH2:4]2)=[C:10]2[C:18]([NH:19][C:20]([CH:22]3[CH2:23][CH2:24]3)=[O:21])=[CH:17][NH:16][C:11]2=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 809722-Bromoethyl methyl etherHCID 81531DiisopropylethylamineHCID 670451631657014-42-0

Product 1

HCID 44515656HCID 44515656, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(R)-N-(4-(3-Aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide hydrochloride (0.100 g, 0.222 mmol; Example 29, Step C), 1-bromo-2-methoxyethane (0.0246 mL, 0.266 mmol), and DIEA (0.154 mL, 0.887 mmol, d 0.742) were placed in DMF (2 mL) and heated to 80° C. for 18 hours. The reaction was then poured into water and extracted with EtOAc. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 20-50% CH3CN/water). The product was next dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give (R)-N-(5-bromo-4-(3-(2-methoxyethylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropane carboxamide (0.03 g, 30%). 1H NMR (400 MHz, D2O) δ 8.23 (s, 1H), 7.26 (s, 1H), 3.77-3.74 (m, 1H), 3.54-3.50 (m, 3H), 3.28-3.11 (m, 5H), 3.18 (s, 3H), 2.19-2.12 (m, 1H), 1.82-1.61 (m, 4H), 0.90-0.82 (m, 4H). LCMS (APCI+) m/z 436, 438 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by reverse phase chromatography (Biotage SP4
  7. dissolutionThe product was next dissolved in minimal DCM (with MeOH to aid solubility)
  8. additionadded to a stirring solution of 1M HCl in ether
  9. filtrationThe resulting solid was filtered
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-cccf894f83fa46e593461d3bb9a10480
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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