Diisopropylethylamine → Benzyl [7-bromo-2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)quinolin-3-yl]carbamate

HRID 924471Notes

Reaction equation

HRID 924471 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][C@H:37]([CH3:39])[C@@H:36]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[C@H:35]([NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[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]([O:40][Si:41]([C:44]([CH3:45])([CH3:46])[CH3:47])([CH3:43])[CH3:42])[C@H:35]([NH:48][C:49]([O:50][C:51]([CH3:52])([CH3:54])[CH3:53])=[O:55])[CH2:34]3)=[O:25])=[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 59226553tert-butyl (3R,4R,5S)-1-(3-aminopyridin-4-yl)-4-(tert-butyldimethylsilyloxy)-5-methylpiperidin-3-ylcarbamateHCID 867268583-{[(Benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid

Product 1

HCID 86726916Benzyl [7-bromo-2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)quinolin-3-yl]carbamateYield 57.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid (0.50 g, 1.2 mmol), tert-butyl ((3R,4R,5S)-1-(3-aminopyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (0.54 g, 1.2 mmol), and HATU (1.2 g, 3.1 mmol) in DMF (4.9 mL) and DIPEA (0.65 mL, 3.7 mmol) was stirred at room temperature for 2 h, then quenched with 50 mL of EtOAc and 30 mL of 1 M NaOH. The resulting layers were separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were concentrated under reduced pressure. The residue was purified by flash chromatography on a 40 g silica gel column, eluting with 0-100% EtOAc in hexanes, to give the sub-title compound (0.565 g, 55%). LCMS calc. for C40H52BrN6O6Si [M+H]+: m/z=919.3. found: 819.4.

Workup

  1. customquenched with 50 mL of EtOAc and 30 mL of 1 M NaOH
  2. customThe resulting layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc
  4. concentrationThe combined organic extracts were concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a 40 g silica gel column
  6. washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-e48cafeb5ed14fd382f18e98d6ca1381
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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