O-Methylhydroxylamine → HCID 73174873, compound

HRID 503211Notes

Reaction equation

HRID 503211 reaction equation
C[CH:2]([O:21][CH2:22]C1NC=CN=1)[C:3]1[CH:4]=[C:5]([N:9]2[C:13]3[CH:14]=[CH:15][C:16]([CH:18]=[N:19][OH:20])=[CH:17][C:12]=3[N:11]=[CH:10]2)[CH:6]=[CH:7][CH:8]=1.CC(OCC1NC=CN=1)C1C=C([N:36]2[C:40]3[CH:41]=[CH:42][C:43]([CH:45]=O)=CC=3N=C2)C=CC=1.CN1C(COCC2C=C(N3C4C=CC(C=NO)=CC=4N=C3)C=CC=2)=NC=N1.CON.CN1C(COCC2C=C(N3C4C=CC(C=NO)=CC=4N=C3)C=CC=2)=CC=N1.S1C=CN=C1COCC1C=C(N2C3C=CC(C=NO)=CC=3N=C2)C=CC=1.S1C=CN=C1COCC1C=C(N2C3C=CC(C=O)=CC=3N=C2)C=CC=1>>[N:36]1[CH:40]=[CH:41][CH:42]=[C:43]([CH2:22][O:21][CH2:2][C:3]2[CH:4]=[C:5]([N:9]3[C:13]4[CH:14]=[CH:15][C:16]([CH:18]=[N:19][OH:20])=[CH:17][C:12]=4[N:11]=[CH:10]3)[CH:6]=[CH:7][CH:8]=2)[CH:45]=1

Participants

8

Reactant 7

HCID 4113O-Methylhydroxylamine3×HCID 73174750HCID 73174750, compoundHCID 73174851HCID 73174851, compoundHCID 73174872HCID 73174872, compoundHCID 86626710HCID 86626710, compoundHCID 86761154HCID 86761154, compoundHCID 87417620HCID 87417620, compound2×

Product 1

HCID 73174873HCID 73174873, compound

Procedure

To a solution of compound 12a (220 mg, 0.64 mmol) and pyridine (0.08 mL, 1.5 equiv) in ethanol (2 mL) was added hydroxylamine hydrochloride (500 mg) and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (100 mL), washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and pet-ether as the eluent to afford compound 14a (180 mg, 78%) as a solid. Mp 154-154.8° C. In analogy herewith, the following compounds were prepared: 1-[3-(1-Methyl-1H-imidazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14b) from 12b. Mp 209.8-211.7° C. and 1-[3-(2-Methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14c) from 12c. Mp 145.8-147.7° C. O-Methyl 1-[3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14h) from 12c and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 377.1724 Da. Calc. 377.172525 Da, dev. −0.3 ppm 1-[3-(2-Methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14e) from 12e. LC-ESI-HRMS of [M+H]+ shows 362.1603 Da. Calc. 362.161625 Da, dev. −3.7 ppm O-Methyl 1-[3-(2-methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14i) from 12e and O-methyl hydroxyl amine. LC-ESI-HRMS of [M+H]+ shows 376.1755 Da. Calc. 376.177325 Da, dev. −4:9 ppm 1-[3-(1,3-Thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14j) from 12g. LC-ESI-HRMS of [M+H]+ shows 365.1074 Da. Calc. 365.107225 Da, dev. 0.5 ppm O-Methyl 1-[3-(1,3-thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14g) from 12g and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 379.1238 Da. Calc. 379.122825 Da, dev. 2.6 ppm and 1-[3-(Pyridin-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14d) 1-[3-(Pyrimidin-4-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14f) are prepared likewise.

Workup

  1. customIn analogy herewith, the following compounds were prepared

Sources & evidence

ORD record
ord-126fb2f366d54c149cf3ba3b00b9ae6b
Source dataset
uspto-grants-2010_08
Patent number
US07776900B2

Reaction notes

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