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

HRID 924461Notes

Reaction equation

HRID 924461 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:29](O)=[O:30])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1[N:39]1[CH2:44][C@H:43]([CH3:45])[CH2:42][C@H:41]([NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])[CH2:40]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>[C:49]([O:48][C:47]([NH:46][C@H:41]1[CH2:42][C@@H:43]([CH3:45])[CH2:44][N:39]([C:38]2[CH:37]=[CH:36][N:35]=[CH:34][C:33]=2[NH:32][C:29]([C:13]2[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)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:40]1)=[O:53])([CH3:50])([CH3:51])[CH3:52]

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 58386794HCID 58386794, compoundHCID 867269043-{[(Benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid

Product 1

HCID 86726905Benzyl [2-{[(4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid (0.014 g, 0.034 mmol), tert-butyl [(3S,5R)-1-(3-aminopyridin-4-yl)-5-methylpiperidin-3-yl]carbamate (0.013 g, 0.041 mmol) and HATU (0.033 g, 0.086 mmol) in DMF (0.14 mL), DIPEA (0.018 mL, 0.10 mmol) was added. The mixture was stirred at room temperature for 2 h, then quenched with 5 mL of EtOAc and 3 mL of 1 M NaOH. The resulting layers were separated and the aqueous phase was further extracted with EtOAc. The combined organic phases were concentrated under reduced pressure. The residue was purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.) to afford the sub-title compound. LCMS calc. for C39H49N8O5 [M+H]+: m/z=709.4. found: 709.5.

Workup

  1. additionwas added
  2. customquenched with 5 mL of EtOAc and 3 mL of 1 M NaOH
  3. customThe resulting layers were separated
  4. extractionthe aqueous phase was further extracted with EtOAc
  5. concentrationThe combined organic phases were concentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC (XBridge™ C18 column
  7. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-23b8591b1ac1438aae54bd53c6288192
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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