Diisopropylethylamine → tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamate

HRID 924527Notes

Reaction equation

HRID 924527 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])[C@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[C@H:41]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[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>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:29]([NH:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][C:38]=2[N:39]2[CH2:44][C@H:43]([CH3:45])[C@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[C@H:41]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:40]2)=[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

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 867269043-{[(Benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acidHCID 86726962tert-butyl methyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate

Product 1

HCID 86726966tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamateYield 49.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid (68 mg, 0.16 mmol), tert-butyl methyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate (62 mg, 0.16 mmol) and HATU (190 mg, 0.500 mmol) in 2 mL of DMF, DIPEA (180 μL, 1.03 mmol) was added. The reaction mixture was stirred at room temperature overnight. The mixture was purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the sub-title compound as a yellow solid (62.4 mg, 49%). LCMS calc. for C41H52N9O7 (M+H)+: m/z=782.4. Found: 782.4.

Workup

  1. additionwas added
  2. customThe mixture was purified by preparative LCMS (pH=10 method
  3. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-7b69a3539378407494e85e015e80176f
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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