Water → HCID 67045247, compound

HRID 1923894Notes

Reaction equation

HRID 1923894 reaction equation
[C:1]([O:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[Br:23][C:24]1[C:25]([N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:40]2)=[C:26]2[C:32]([NH:33][C:34]([CH:36]3[CH2:38][CH2:37]3)=[O:35])=[CH:31][NH:30][C:27]2=[N:28][CH:29]=1.O>CN(C1C=CN=CC=1)C.ClCCl>[C:9]([O:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10].[Br:23][C:24]1[C:25]([N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46]([O:47][C:48]([CH3:49])([CH3:51])[CH3:50])=[O:52])[CH2:40]2)=[C:26]2[C:32]([NH:33][C:34]([CH:36]3[CH2:38][CH2:37]3)=[O:35])=[CH:31][N:30]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[C:27]2=[N:28][CH:29]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 90495Di-tert-butyl dicarbonateHCID 67045318HCID 67045318, compound

Product 2

HCID 90495Di-tert-butyl dicarbonateHCID 67045247HCID 67045247, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

di-tert-Butyl dicarbonate (150 mg, 0.687 mmol), DMAP (21 mg, 0.172 mmol) and triethylamine (174 mg, 0.239 mL, 1.72 mmol) were added to a solution of (R)-tert-butyl 1-(5-bromo-3-(cyclopropane carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (274 mg, 0.573 mmol; Example 29, Step B) in anhydrous dichloromethane (6 mL). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. The mixture was concentrated. The residue was taken up in EtOAc, washed with water (3×10 mL) and brine (3×10 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 20-95% CH di-tert-butyl dicarbonate (150 mg, 0.687 mmol), DMAP (21 mg, 0.172 mmol) and triethylamine (174 mg, 0.239 mL, 1.72 mmol)CN/water, 25CV) to give (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(cyclopropane carboxamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (237 mg, 71% yield) as a solid. 1H NMR (400 MHz, CDCl3) δ 10.03 (br s, 1H), 8.48 (s, 1H), 8.19 (s, 1H), 3.93-3.73 (m, 1H), 3.67-3.45 (m, 1H), 3.41-3.30 (m, 1H), 3.06-2.99 (m, 1H), 2.27-2.17 (m, 1H), 2.06-1.95 (m, 1H), 1.90-1.77 (m, 1H), 1.63 (s, 9H), 1.60 (s, 1H), 1.42 (s, 9H), 1.22-1.05 (m, 2H), 1.03-0.85 (m, 2H). LCMS (APCI+) m/z 580 (M+2H)+, Retention time=4.53 minutes.

Workup

  1. concentrationThe mixture was concentrated
  2. washwashed with water (3×10 mL) and brine (3×10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-b823f733d6804079b470f062a69c2309
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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