Hydrochloric Acid → HCID 10257955, compound

HRID 131250Notes

Reaction equation

HRID 131250 reaction equation
[CH:1]1([C:4]([N:6]([C:12]2[CH:22]=[CH:21][C:15]([C:16]([O:18]CC)=O)=[CH:14][CH:13]=2)[CH2:7][CH2:8][N:9]([CH3:11])[CH3:10])=[O:5])[CH2:3][CH2:2]1.[OH-].[Na+].Cl.Cl.Cl.[CH2:28]([O:30][C:31]1[CH:32]=[C:33]([CH:50]=[CH:51][CH:52]=1)[CH2:34][N:35]1[C:39]2=[N:40][CH:41]=[N:42][C:43]([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)=[C:38]2[CH:37]=[N:36]1)[CH3:29].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>C(O)C.C(Cl)(Cl)Cl.C(N(CC)CC)C.C(Cl)Cl>[CH2:28]([O:30][C:31]1[CH:32]=[C:33]([CH:50]=[CH:51][CH:52]=1)[CH2:34][N:35]1[C:39]2=[N:40][CH:41]=[N:42][C:43]([N:44]3[CH2:45][CH2:46][N:47]([C:16](=[O:18])[C:15]4[CH:14]=[CH:13][C:12]([N:6]([C:4]([CH:1]5[CH2:2][CH2:3]5)=[O:5])[CH2:7][CH2:8][N:9]([CH3:10])[CH3:11])=[CH:22][CH:21]=4)[CH2:48][CH2:49]3)=[C:38]2[CH:37]=[N:36]1)[CH3:29]

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69298924HCID 69298924, compoundHCID 69301231HCID 69301231, compound

Product 1

HCID 10257955HCID 10257955, compoundYield 84%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of ethyl 4-[N-(cyclopropylcarbonyl)-N-[2-(dimethylamino)ethyl]-amino]benzoate (106 mg; compound obtained in Reference Example 11) in ethanol (3 mL) is added 2N sodium hydroxide solution (21 μL) and the mixture is stirred at room temperature overnight. To the reaction mixture is added 2N HCl (42 μL) and the mixture is concentrated to give a crude carboxylic acid compound. To the compound is added successively methylene chloride (2 mL), 1-(3-ethoxybenzyl)-4-piperazin-1-yl-1H-pyrazolo[3,4-d]pyrimidine dihydrochloride (105 mg, compound described in WO02/79189), 1-hydroxybenzotriazole (51.7 mg), triethylamine (124.5 μL) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (73.4 mg) and the mixture is stirred at room temperature for 19 hours. The reaction mixture is diluted with chloroform (5 mL) and thereto is added a saturated sodium hydrogencarbonate solution (10 mL). After stirring, the organic layer is separated and concentrated. The resultant crude product is purified by flash column chromatography on NH-silica gel (Chromatorex NH silica gel; Fuji Silicia Chemical Ltd., Solvent; ethyl acetate:chloroform=1:0→0:1) to give 1-(3-ethoxybenzyl)-4-[4-[4-[N-(cyclopropyl-carbonyl)-N-[2-(dimethylamino)ethyl]amino]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine (127 mg, yield; 84%) as an amorphous powder. MS (APCI) m/z: 597 [M+H]+

Workup

  1. concentrationthe mixture is concentrated
  2. customto give a crude carboxylic acid compound
  3. stirringthe mixture is stirred at room temperature for 19 hours
  4. stirringAfter stirring
  5. customthe organic layer is separated
  6. concentrationconcentrated
  7. customThe resultant crude product is purified by flash column chromatography on NH-silica gel (Chromatorex NH silica gel; Fuji Silicia Chemical Ltd., Solvent; ethyl acetate:chloroform=1:0→0:1)

Sources & evidence

ORD record
ord-59ed2460fac344e882eff353e1937609
Source dataset
uspto-grants-2008_06
Patent number
US07384952B2

Reaction notes

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