Ammonia → HCID 178509943, compound

HRID 1875228Notes

Reaction equation

HRID 1875228 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH2:37]O)[N:5](COCC[Si](C)(C)C)[C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[C:21]([Cl:27])[CH:20]=2)[C:12]=1[F:28])=[O:8].CC[N:41](C(C)C)C(C)C.N>CN(C=O)C.CO>[NH2:41][CH2:37][C:4]1[NH:5][C:6]([C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]3[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[C:21]([Cl:27])[CH:20]=3)[C:12]=2[F:28])=[O:8])=[C:2]([Br:1])[N:3]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 68724305HCID 68724305, compound

Product 1

HCID 178509943HCID 178509943, compoundYield 5.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ms-CI (0.023 ml, 0.30 mmol) was added to a solution of 4-bromo-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-(hydroxymethyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (0.097 g, 0.15 mmol) and DIEA (0.26 ml, 1.50 mmol) in DMF (1 ml) and the reaction mixture was stirred at room temperature for 1 h. Ammonia (1 ml of a 7M solution in methanol, 7.00 mmol) was added and stirring was continued overnight. Deprotection using similar procedures as that described herein and purification by Reverse-Phase HPLC (water:acetonitrile with 0.1% NH4OH) provided the title compound (0.004 g, 5%) as an off-white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.32 (br. s., 1H), 7.56 (s, 1H), 7.33-7.45 (m, 2H), 7.28 (br. s., 1H), 7.21 (s, 1H), 4.65 (br. s., 2H), 4.19 (s, 2H). ES-LCMS: m/z 511.9, 513.9, 515.9 (M+1).

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. customherein and purification by Reverse-Phase HPLC (water:acetonitrile with 0.1% NH4OH)

Sources & evidence

ORD record
ord-70bf1a4f9a9f40dfb484f5bc99738a4d
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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