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

HRID 924523Notes

Reaction equation

HRID 924523 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:9]([O:16][C:17]([NH:19][C:20]1[C:21]([C:31]([NH:33][C:34]2[CH:35]=[N:36][CH:37]=[CH:38][C:39]=2[N:40]2[CH2:45][C@H:44]([CH3:46])[C@H:43]([NH:47][C:48](=[O:51])[O:49][CH3:50])[C@H:42]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:41]2)=[O:32])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[C:25](Br)[CH:24]=2)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH3:60][C:61]1(C)C(C)(C)OB(C=C)O1.O>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>[CH2:9]([O:16][C:17]([NH:19][C:20]1[C:21]([C:31]([NH:33][C:34]2[CH:35]=[N:36][CH:37]=[CH:38][C:39]=2[N:40]2[CH2:45][C@H:44]([CH3:46])[C@H:43]([NH:47][C:48](=[O:51])[O:49][CH3:50])[C@H:42]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:41]2)=[O:32])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[C:25]([CH:60]=[CH2:61])[CH:24]=2)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 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 86726963tert-Butyl methyl [(3R,4S,5S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-7-vinylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)-5-methylpiperidine-3, 4-diyl]biscarbamateYield 49.5%

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A vial was charged with dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (40 mg, 0.051 mmol), and K3PO4 (179 mg, 0.844 mmol) were added. The vial was sealed with a septum, then purged with nitrogen three times. A mixture 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) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (87 mg, 0.56 mmol) in 1,4-dioxane (2.0 mL) was added, followed by deoxygenated water (0.50 mL, 28 mmol). The resulting 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 (92 mg, 49%). LCMS calc. for C38H44N7O7 (M+H)+: m/z=710.3. Found: 710.3.

Workup

  1. additionwere added
  2. customThe vial was sealed with a septum
  3. custompurged with nitrogen three times
  4. additionwas added
  5. customThe resulting reaction mixture
  6. customThe mixture was purified by preparative LCMS (pH=10 method
  7. 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-567e5f113a724ce4b98c824c7c33051f
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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