1-Hydroxybenzotriazole → HCID 178494080, compound

HRID 531290Notes

Reaction equation

HRID 531290 reaction equation
[F:1][C:2]([F:51])([F:50])[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[CH2:47][CH:46]([F:48])[CH2:45]4)[N:21]=3)[C@H:14]2[CH3:49])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.O.[NH2:72][C:73]1[NH:77][N:76]=[N:75][N:74]=1>CN(C=O)C.C(Cl)CCl>[F:1][C:2]([F:50])([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]([NH:72][C:73]6[NH:77][N:76]=[N:75][N:74]=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[CH2:45][CH:46]([F:48])[CH2:47]4)[N:21]=3)[C@H:14]2[CH3:49])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 72189373HCID 72189373, compoundHCID 178509300HCID 178509300, compound

Product 1

HCID 178494080HCID 178494080, compoundYield 66.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 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-(3-fluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoic acid (EXAMPLE 36, 167 mg, 0.232 m mol), EDC (90 mg, 0.464 m mol), HOBt (60 mg, 0.437 m mol), and DIEA (81 μl, 0.464 m mol) in DMF (2 mL) was added 5-aminotetrazole monohydrate (120 mg, 1.16 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 get the title compound (121 mg, 43% yield), as a white solid after lyophilization. LCMS (M+H)+: 787.2. 1H NMR (DMSO-d6, 500 MHz): δ 12.44 (s, 1H), 8.31 (s, 1H), 8.29 (d, 3.5 Hz, 1H), 8.12 (s, 1H), 8.09 (s, 1H), 8.00 (m, 3H), 7.82 (d, 2.0 Hz, 1H), 7.50 (d, 8.0 Hz, 1H), 5.91 (d, 8.5 Hz, 1H), 5.59 (m, 1H), 4.53 (d, 17.0 Hz, 1H), 4.49-4.38 (m, 3H), 4.22-4.07 (m, 3H), 3.93 (s, 3H), 2.40 (s, 3H), 0.64 (d, 6.5 Hz, 3H). RTA IC50: 10 nM.

Workup

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

Sources & evidence

ORD record
ord-8f96c44f49e04907b67e4f2a8e7aa4df
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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