Diisopropylethylamine → Benzyl [(3S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-bromoquinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate

HRID 924366Notes

Reaction equation

HRID 924366 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([OH:25])=O)=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([Br:22])[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][C:32]=1[N:33]1[CH2:38][CH2:37][CH2:36][C@H:35]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:34]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([NH:26][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][C:32]=2[N:33]2[CH2:38][CH2:37][CH2:36][C@H:35]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH2:34]2)=[O:25])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([Br:22])[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86726856Benzyl [(3S)-1-(3-aminopyridin-4-yl)piperidin-3-yl]carbamateHCID 867268583-{[(Benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid

Product 1

HCID 86726859Benzyl [(3S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-bromoquinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid (632.0 mg, 1.575 mmol), benzyl [(3S)-1-(3-aminopyridin-4-yl)piperidin-3-yl]carbamate (559.9 mg, 1.715 mmol) and HATU (1822 mg, 4.792 mmol), DMF (15.0 mL) was added, followed by DIPEA (1854 mg, 14.34 mmol). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure. The residue was dissolved in EtOAc (100 mL), washed with brine (2×100 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM) to afford the sub-title compound (912.7 mg, 82%). LCMS calc. for C36H34BrN6O5(M+H)+: m/z=709.2. found 709.1.

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in EtOAc (100 mL)
  4. washwashed with brine (2×100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-046432238bec4de2b70df43185d47daa
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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