Acetone → HCID 67045360, compound

HRID 408172Notes

Reaction equation

HRID 408172 reaction equation
CCN(C(C)C)[CH:4]([CH3:6])[CH3:5].[ClH:10].[NH2:11][CH2:12][C@@H:13]1[CH2:17][CH2:16][N:15]([C:18]2[C:23]([Br:24])=[CH:22][N:21]=[C:20]3[NH:25][CH:26]=[C:27]([NH:28][C:29](=[O:36])[C:30]4[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=4)[C:19]=23)[CH2:14]1.CC(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CN(C=O)C>[ClH:10].[Br:24][C:23]1[C:18]([N:15]2[CH2:16][CH2:17][C@@H:13]([CH2:12][NH:11][CH:4]([CH3:6])[CH3:5])[CH2:14]2)=[C:19]2[C:27]([NH:28][C:29](=[O:36])[C:30]3[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=3)=[CH:26][NH:25][C:20]2=[N:21][CH:22]=1

Participants

7

Reactant 5

HCID 180AcetoneHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67045227HCID 67045227, compound

Product 1

HCID 67045360HCID 67045360, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

DIEA (0.023 mL, 0.133 mmol) was added to a solution of (S)—N-(4-(3-(aminomethyl)pyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (70 mg, 0.13 mmol; Example 3A) and propan-2-one (77.4 mg, 1.33 mmol) in CH2Cl2:DMF (1:1, 3 mL), followed by the addition of NaBH(OAc)3 (57 mg, 0.26 mmol). The reaction was stirred for 30 minutes. The reaction mixture was then poured into a solution of Na2CO3 and extracted into CH2Cl2. The organic phases were combined, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC (Gilson system). The isolated product was then dissolved in minimal CH2Cl2 (with MeOH to aid solubility) and added to 1M HCl in ether (10 mL). The solid formed was collected to provide (S)—N-(5-bromo-4-(3-((isopropylamino)methyl)pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (40 mg, 53% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.08 (d, 1H), 10.58 (s, 1H), 9.32 (d, 1H), 8.98 (dd, 1H), 8.76 (dt, 1H), 8.32 (s, 1H), 7.99 (dd, 1H), 7.67 (d, 1H), 3.77-3.73 (m, 1H), 3.60-3.52 (m, 2H), 3.39-3.34 (m, 1H), 3.23-3.16 (m, 1H), 2.91-2.85 (m, 2H), 2.73-2.66 (m, 1H), 2.14-2.07 (m, 1H), 1.74-1.64 (m, 1H), 1.22 (d, 6H); LCMS (APCI+) m/z 459.1, 460.1 (M+H)+.

Workup

  1. extractionextracted into CH2Cl2
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase HPLC (Gilson system)
  6. dissolutionThe isolated product was then dissolved in minimal CH2Cl2 (with MeOH to aid solubility)
  7. additionadded to 1M HCl in ether (10 mL)
  8. customThe solid formed
  9. customwas collected

Sources & evidence

ORD record
ord-8ec588a4ce174d21adf26fcc74f56525
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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