Diisopropylethylamine → Benzyl [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]-7-(4-methyl-3-oxopiperazin-1-yl)quinolin-3-yl]carbamate

HRID 924506Notes

Reaction equation

HRID 924506 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:30](O)=[O:31])=[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])[C:24](=[O:29])[CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:33][C:34]1[CH:35]=[N:36][CH:37]=[CH:38][C:39]=1[N:40]1[CH2:45][C@H:44]([CH3:46])[C@H:43]([N:47]2[CH:51]=[CH:50][N:49]=[N:48]2)[C@H:42]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:41]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.CO.O>[C:55]([O:54][C:53]([NH:52][C@H:42]1[C@@H:43]([N:47]2[CH:51]=[CH:50][N:49]=[N:48]2)[C@@H:44]([CH3:46])[CH2:45][N:40]([C:39]2[CH:38]=[CH:37][N:36]=[CH:35][C:34]=2[NH:33][C:30]([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])[C:24](=[O:29])[CH2:23]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:31])[CH2:41]1)=[O:59])([CH3:56])([CH3:57])[CH3:58]

Participants

8

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 867269303-{[(Benzyloxy)carbonyl]amino}-7-(4-methyl-3-oxopiperazin-1-yl)quinoline-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 86726947Benzyl [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]-7-(4-methyl-3-oxopiperazin-1-yl)quinolin-3-yl]carbamateYield 57%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(4-methyl-3-oxopiperazin-1-yl)quinoline-2-carboxylic acid (12.2 mg, 0.028 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 (10.0 mg, 0.027 mmol), HATU (33 mg, 0.087 mmol), in DMF (0.29 mL), DIPEA (0.018 mL, 0.10 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was diluted with MeOH and H2O, filtered and the filtrate was purified by preparative LCMS (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.) to give the sub-title compound as a bright yellow powder (12 mg, 57%). LCMS calc. for C41H48N11O6 (M+H)+: m/z=790.4. Found: 790.3.

Workup

  1. filtrationfiltered
  2. customthe filtrate was purified by preparative LCMS (XBridge™ C18 column
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.)

Sources & evidence

ORD record
ord-52746dffa770447d8af92bea13b5b20c
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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