HCID 12665370, compound → Urea

HRID 418363Notes

Reaction equation

HRID 418363 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:32])[NH:11][CH2:12][C:13]2[CH:14]=[C:15]([CH:29]=[CH:30][CH:31]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:22][N:23]([CH3:28])[CH2:24][CH2:25][C:26]=3[N:27]=2)=[O:17])[CH:6]=[CH:7][CH:8]=1)#[CH:2].C(NC1C=CC=CC=1)#C>>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:32])[NH:11][CH2:12][C:13]2[CH:14]=[C:15]([CH:29]=[CH:30][CH:31]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:22][N:23]([CH3:28])[CH2:24][CH2:25][C:26]=3[N:27]=2)=[O:17])[CH:6]=[CH:7][CH:8]=1)#[CH:2].[NH2:9][C:10]([NH2:11])=[O:32]

Participants

4

Reactant 2

HCID 12665370HCID 12665370, compoundHCID 59190899HCID 59190899, compound

Product 2

HCID 1176UreaHCID 59190899HCID 59190899, compound

Procedure

3-Ethynlaniline (0.15 mL, 1.43 mmol) was added to a 20% solution of phosgene in toluene (4.04 mmol) followed by DIPEA (0.50 mL, 2.71 mmol). The reaction mixture was stirred at room temperature for 3 h. To this was added 3-aminomethyl-N-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-benzamide (250 mg, 0.69 mmol) and 1 mL of DMSO. The reaction mixture was stirred overnight at room temperature, then diluted with EtOAc (100 mL), washed with water (2×100 mL), dried with Na2SO4 and concentrated to provide 300 mg of a yellow solid. LC-MS indicated this was a mixture of primarily desired product and the symmetrical urea of ethynyl aniline. This material was triturated with methanol which enriched the ppt in desired product (now approximately 40%) and removed the residual amine. This solid was then partitioned between ethyl acetate and 2 N HCl. The aqueous phase was separated, neutralized, and extracted with ethyl acetate to provide a mixture ˜9:1 of the desired product and urea (25 mg yellow solid). This material was further purified by prep HPLC to provide 3 mg of 3-[3-(3-ethynyl-phenyl)-ureidomethyl]-N-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-benzamide. MS, electrospray, 447 (M+H).

Workup

  1. customThis material was triturated with methanol which
  2. customremoved the residual amine
  3. customThis solid was then partitioned between ethyl acetate and 2 N HCl
  4. customThe aqueous phase was separated
  5. extractionextracted with ethyl acetate

Sources & evidence

ORD record
ord-d679bb3277cc4483a679e9425566c416
Source dataset
uspto-grants-2012_01
Patent number
US08093266B2

Reaction notes

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