1,2-Dichloroethane → HCID 178494081, compound

HRID 531297Notes

Reaction equation

HRID 531297 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:42]=[CH:41][C:37]([C:38](O)=[O:39])=[CH:36][C:35]=5[CH3:43])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.O.[NH2:77][C:78]1[NH:82][N:81]=[N:80][N:79]=1>CN(C=O)C>[F:51][C:2]([F:1])([F:52])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:42]=[CH:41][C:37]([C:38]([NH:77][C:78]6[NH:82][N:81]=[N:80][N:79]=6)=[O:39])=[CH:36][C:35]=5[CH3:43])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 72189372HCID 72189372, compoundHCID 178509300HCID 178509300, compound

Product 1

HCID 178494081HCID 178494081, compoundYield 72.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(morpholin-4-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoic acid (EXAMPLE 39, 195 mg, 0.276 mmol), EDC (106 mg, 0.55 mmol), HOBt (56 mg, 0.42 mmol), and DIEA (96 μl, 0.55 mmol) in DMF (2 mL) was added 5-aminotetrazole monohydrate (144 mg, 1.38 mmol). After stirring at 40° C. for 8 hours, the reaction mixture was directly applied to reverse phase HPLC, eluting with 10% to 100% acetonitrile in water, to obtain the title compound (160 mg, 57% yield), as a white solid after lyophilization. LCMS (M+H)+: 799.1. 1H NMR (DMSO-d6, 500 MHz): δ 12.44 (s, 1H), 8.31 (s, 1H), 8.28 (d, J=2.5 Hz, 1H), 8.13 (s, 1H), 8.08 (s, 1H), 7.99 (m, 1H), 7.98 (s, 2H), 7.82 (d, J=2.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 5.89 (d, J=8.5 Hz, 1H), 4.54 (d, J=17.0 Hz, 1H), 4.34 (m, 1H), 4.05 (d, J=17.0 Hz, 1H), 3.93 (s, 3H), 3.76 (m, 4H), 3.70 (m, 4H), 2.40 (s, 3H), 0.62 (d, J=6.5 Hz, 3H). RTA IC50: 11 nM

Workup

  1. washeluting with 10% to 100% acetonitrile in water

Sources & evidence

ORD record
ord-50af2b539cad43b28816b4767cca1e3a
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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