Azetidine → (R)-tert-butyl 1-(3-(azetidine-1-carboxamido)-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 2204006Notes

Reaction equation

HRID 2204006 reaction equation
N1(C(N2C=CN=C2)=O)C=CN=C1.NC1C2C(=NC=C(Br)C=2N2CCC[C@@H](NC(=O)OC(C)(C)C)C2)NC=1.N1CCC1.[Br:42][C:43]1[C:44]([N:60]2[CH2:65][CH2:64][CH2:63][C@@H:62]([NH:66][C:67](=[O:73])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70])[CH2:61]2)=[C:45]2[C:51]([NH:52][C:53]([N:55]3[CH:59]=[CH:58]N=[CH:56]3)=[O:54])=[CH:50][NH:49][C:46]2=[N:47][CH:48]=1>C1COCC1>[N:55]1([C:53]([NH:52][C:51]2[C:45]3[C:46](=[N:47][CH:48]=[C:43]([Br:42])[C:44]=3[N:60]3[CH2:65][CH2:64][CH2:63][C@@H:62]([NH:66][C:67](=[O:73])[O:68][C:69]([CH3:71])([CH3:70])[CH3:72])[CH2:61]3)[NH:49][CH:50]=2)=[O:54])[CH2:59][CH2:58][CH2:56]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 682631,1'-CarbonyldiimidazoleHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateHCID 67045556(R)-tert-butyl 1-(5-bromo-3-(1H-imidazole-1-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045546(R)-tert-butyl 1-(3-(azetidine-1-carboxamido)-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Di(1H-imidazol-1-yl)methanone (3.2 g, 19 mmol) was added to (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (2.0 g, 4.9 mmol; Example 98, Step A) in THF (100 mL), and the reaction mixture was stirred at room temperature for 18 hours. The reaction solution was used as is. Azetidine (113 mg, 1.98 mmol) was added to (R)-tert-butyl 1-(5-bromo-3-(1H-imidazole-1-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (200 mg, 0.397 mmol) in THF (20 mL), and the reaction was stirred for 18 hours. The reaction was concentrated to dryness and then purified by reverse phase chromatography (SP4, 25M, water/ACN 90/10→0/100, 30 CV) to yield (R)-tert-butyl 1-(3-(azetidine-1-carboxamido)-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (90 mg, 46.0% yield) as a solid.

Workup

  1. stirringthe reaction was stirred for 18 hours
  2. concentrationThe reaction was concentrated to dryness
  3. custompurified by reverse phase chromatography (SP4, 25M, water/ACN 90/10→0/100, 30 CV)

Sources & evidence

ORD record
ord-b672389a4e2e42948828599b1d441eed
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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