Sodium Iodide → (R)-6-[[3-[[4-[2-[[2-[8-(Benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl]-2-[(tert-butyldimethylsilyl)oxy]ethyl]amino]ethyl]phenyl]carbamoyl]-phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide

HRID 1944950Notes

Reaction equation

HRID 1944950 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([S:19]([C:22]3[CH:23]=[C:24]4[C:29](=[C:30]([CH3:32])[CH:31]=3)[N:28]=[CH:27][C:26]([C:33]([NH2:35])=[O:34])=[C:25]4[NH:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=3)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=2)=[O:12])=[CH:6][CH:5]=1.[CH2:45]([O:52][C:53]1[CH:54]=[CH:55][C:56]([C@@H:64]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])[CH2:65]Br)=[C:57]2[C:62]=1[NH:61][C:60](=[O:63])[CH:59]=[CH:58]2)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[I-].[Na+].C([O-])([O-])=O.[K+].[K+]>O.CN(C=O)C.C(#N)C>[CH2:45]([O:52][C:53]1[CH:54]=[CH:55][C:56]([C@@H:64]([O:67][Si:68]([C:71]([CH3:72])([CH3:74])[CH3:73])([CH3:70])[CH3:69])[CH2:65][NH:1][CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]3[CH:14]=[C:15]([S:19]([C:22]4[CH:23]=[C:24]5[C:29](=[C:30]([CH3:32])[CH:31]=4)[N:28]=[CH:27][C:26]([C:33]([NH2:35])=[O:34])=[C:25]5[NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=4)(=[O:20])=[O:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:6][CH:5]=2)=[C:57]2[C:62]=1[NH:61][C:60](=[O:63])[CH:59]=[CH:58]2)[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneHCID 585050736-[[3-[[4-(2-Aminoethyl)phenyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide

Product 1

HCID 86659112(R)-6-[[3-[[4-[2-[[2-[8-(Benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl]-2-[(tert-butyldimethylsilyl)oxy]ethyl]amino]ethyl]phenyl]carbamoyl]-phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Intermediate 94 (206 mg, 0.258 mmol) was combined with (R)-8-(benzyloxy)-5-[2-bromo-1-[(tert-butyldimethylsilyl)oxy]ethyl]quinolin-2(1H)-one (115 mg, 0.235 mmol), sodium iodide (20 mg, 0.133 mmol), and K2CO3 (97 mg, 0.705 mmol) in a mixture of anhydrous acetonitrile (1.0 mL) and anhydrous DMF (0.5 mL) and was heated to 100° C. in a microwave for 2 h. The reaction was poured into H2O and extracted repeatedly into EtOAc. Flash chromatography (0-15% MeOH/CH2Cl2) gave the title compound as a yellow solid, 98 mg. 1H NMR (400 MHz, DMSO-d6) δ 10.81 (s, 1H), 10.54 (br s, 1H), 10.45 (s, 1H), 9.09 (s, 1H), 8.36 (d, J=1.7 Hz, 1H), 8.29-8.34 (m, 2H), 8.27 (d, J=10.0 Hz, 1H), 8.21 (dt, J=7.8, 1.3 Hz, 1H), 8.02-8.05 (m, 1H), 7.85-7.89 (m, 1H), 7.78 (br s, 1H), 7.75 (t, J=7.9 Hz, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.54-7.58 (m, 2H), 7.33-7.40 (m, 2H), 7.27-7.33 (m, 1H), 7.14-7.20 (m, 3H), 7.11 (t, J=8.1 Hz, 1H), 7.09 (d, J=8.3 Hz, 1H), 6.62-6.68 (m, 2H), 6.54 (d, J=9.9 Hz, 1H), 6.50-6.54 (m, 1H), 5.26 (s, 2H), 5.09-5.17 (m, 1H), 3.60 (s, 3H), 2.72-2.86 (m, 3H), 2.71 (s, 3H), 2.59-2.68 (m, 3H), 0.78 (s, 9H), 0.00 (s, 3H), −0.21 (s, 3H). ES/MS calcd. for C57H61N6O8Ssi+ 1017.4. Found m/z=1017.5 (M+H+).

Workup

  1. extractionextracted repeatedly into EtOAc

Sources & evidence

ORD record
ord-9efe5c880533400ea4225fb743eaa39f
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

Loading…