Hydrochloric Acid → HCID 71293612, compound

HRID 1402601Notes

Reaction equation

HRID 1402601 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:42]=[CH:41][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([NH:31][CH:32]([CH2:36][CH2:37][C:38](O)=[O:39])[C:33]([OH:35])=O)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11].Cl.C[N:45](C)[CH2:46][CH2:47]CN=C=NCC.[CH2:55]1[CH2:59]OCC1.Cl.C[N:62](C=O)C>O>[CH2:46]([NH:45][C:33](=[O:35])[CH:32]([NH:31][C:29]([C:26]1[CH:25]=[C:24]([C:20]2[CH:19]=[C:18]([O:17][C:16]3[CH:41]=[CH:42][C:13]([NH:12][C:10]([NH:9][C:3]4[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=4[F:1])=[O:11])=[CH:14][CH:15]=3)[CH:23]=[CH:22][N:21]=2)[NH:28][CH:27]=1)=[O:30])[CH2:36][CH2:37][C:38]([NH:62][CH2:59][CH3:55])=[O:39])[CH3:47]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67042306HCID 67042306, compound

Product 1

HCID 71293612HCID 71293612, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 2-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanedioic acid (Example 63) (100 mg, 0.17 mmol) in 10 ml of anhydrous DMF was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 84 mg, 0.44 mmol). The mixture was stirred at room temperature for 30 minutes, followed by addition of 2-Methylamine solution in THF (0.45 ml, 0.90 mmol). The mixture was stirred for another 16 hours, and poured into 100 ml of water with vigorous stirring. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried to give the crude, which was purified by silica gel chromatography eluting with 3˜5% of methanol in chloroform to afford N,N′-diethyl-2-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanediamide as white solid. Yield: 60 mg, 55%.

Workup

  1. stirringThe mixture was stirred for another 16 hours
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried
  5. customto give the crude, which
  6. customwas purified by silica gel chromatography
  7. washeluting with 3˜5% of methanol in chloroform

Sources & evidence

ORD record
ord-38cd3285333f476e86f6c79f9498c464
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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