Potassium Phosphate, Tribasic → tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamate

HRID 924531Notes

Reaction equation

HRID 924531 reaction equation
[CH3:1][N:2]1[CH2:7][CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH2:4][CH2:3]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:25]([O:32][C:33]([NH:35][C:36]1[C:37]([C:47]([NH:49][C:50]2[CH:51]=[N:52][CH:53]=[CH:54][C:55]=2[N:56]2[CH2:61][C@H:60]([CH3:62])[C@H:59]([NH:63][C:64](=[O:67])[O:65][CH3:66])[C@H:58]([NH:68][C:69](=[O:75])[O:70][C:71]([CH3:74])([CH3:73])[CH3:72])[CH2:57]2)=[O:48])=[N:38][C:39]2[C:44]([CH:45]=1)=[CH:43][CH:42]=[C:41](Br)[CH:40]=2)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCOCC1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[CH2:25]([O:32][C:33]([NH:35][C:36]1[C:37]([C:47]([NH:49][C:50]2[CH:51]=[N:52][CH:53]=[CH:54][C:55]=2[N:56]2[CH2:61][C@H:60]([CH3:62])[C@H:59]([NH:63][C:64](=[O:67])[O:65][CH3:66])[C@H:58]([NH:68][C:69](=[O:75])[O:70][C:71]([CH3:74])([CH3:73])[CH3:72])[CH2:57]2)=[O:48])=[N:38][C:39]2[C:44]([CH:45]=1)=[CH:43][CH:42]=[C:41]([C:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH:4]=1)[CH:40]=2)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 86726961tert-Butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-bromoquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3, 4-diyl]biscarbamate

Product 1

HCID 86726970tert-Butyl methyl {(3R,4S,5S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]-5-methylpiperidine-3, 4-diyl}biscarbamateYield 19.6%

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A vial was charged with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (107 mg, 0.477 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (36 mg, 0.046 mmol), and K3PO4 (175 mg, 0.824 mmol). The vial was sealed with a septum and purged with nitrogen three times. A solution of tert-butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-bromoquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate (200 mg, 0.262 mmol) in 1,4-dioxane (2.0 mL) was added, followed by deoxygenated water (0.50 mL). The reaction mixture was heated at 60° C. for 2 h. 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 (40 mg, 19%). LCMS calc. for C42H51N8O7 (M+H)+: m/z=779.4. Found: 779.4.

Workup

  1. customThe vial was sealed with a septum
  2. custompurged with nitrogen three times
  3. customby deoxygenated water (0.50 mL)
  4. customThe mixture was purified by preparative LCMS (pH=10 method
  5. 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-47ee8c6bd1124400b3c74f227a2c212e
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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