Diisopropylethylamine → Benzyl {7-bromo-2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamate

HRID 924508Notes

Reaction equation

HRID 924508 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23](O)=[O:24])=[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][C@H:37]([CH3:39])[C@H:36]([N:40]2[CH:44]=[CH:43][N:42]=[N:41]2)[C@H:35]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[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>[Br:22][C:17]1[CH:16]=[C:15]2[C:20]([CH:21]=[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:13]([C:23]([NH:26][C:27]3[CH:28]=[N:29][CH:30]=[CH:31][C:32]=3[N:33]3[CH2:38][C@H:37]([CH3:39])[C@H:36]([N:40]4[CH:44]=[CH:43][N:42]=[N:41]4)[C@H:35]([NH:45][C:46]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:52])[CH2:34]3)=[O:24])=[N:14]2)=[CH:19][CH:18]=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 867268583-{[(Benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acidHCID 86726946tert-Butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate

Product 1

HCID 86726948Benzyl {7-bromo-2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamateYield 131%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid (47 mg, 0.12 mmol), tert-butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate (40 mg, 0.11 mmol), and HATU (100 mg, 0.27 mmol), in DMF (0.4 mL), DIPEA (0.056 mL, 0.32 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated under reduced pressure. After concentration, the residue was purified by flash chromatography on silica using a CombiFlash® apparatus (0-100% EtOAc in hexanes) to give the sub-title compound as a light yellow powder (109 mg). LCMS calc. for C36H39BrN9O5 (M+H)+: m/z=756.2. Found: 756.3.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. concentrationAfter concentration
  3. customthe residue was purified by flash chromatography on silica using a CombiFlash® apparatus (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-36e9b4328c534189b0a401eeadd6256a
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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