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

HRID 924466Notes

Reaction equation

HRID 924466 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]([C:39]([F:42])([F:41])[F:40])[CH2:36][C@H:35]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[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]([C:39]([F:41])([F:40])[F:42])[CH2:36][C@H:35]([NH:43][C:44]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:50])[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 86726900tert-Butyl ((3S,5R)-1-(3-aminopyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl)carbamate

Product 1

HCID 86726911Benzyl {7-bromo-2-[({4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamateYield 55.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylic acid (0.50 g, 1.2 mmol), tert-butyl [(3S,5R)-1-(3-aminopyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (0.45 g, 1.2 mmol) and HATU (1.2 g, 3.1 mmol) in DMF (4.9 mL), DIPEA (0.65 mL, 3.7 mmol) was added. The mixture was stirred at room temperature for 2 h, then quenched with 50 mL of EtOAc and 30 mL of 1 M NaOH. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organics 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 (0.492 g, 53%). LCMS calc. for C34H35BrF3N6O5 [M+H]+: m/z=743.2. found: 743.3.

Workup

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

Sources & evidence

ORD record
ord-03f0dc1fccf74ffc81d7be9fb2f923dc
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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