Piperidin-4-ol → HCID 57597385, compound

HRID 1925944Notes

Reaction equation

HRID 1925944 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][C:28]4[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=4)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[OH:37][CH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][C:28]4[CH:36]=[CH:35][C:31]([C:32]([N:41]5[CH2:42][CH2:43][CH:38]([OH:37])[CH2:39][CH2:40]5)=[O:34])=[CH:30][CH:29]=4)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

7

Reactant 4

HCID 79341Piperidin-4-olHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57597378HCID 57597378, compound

Product 1

HCID 57597385HCID 57597385, compoundYield 96.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-{[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}benzoic acid (150 mg), 4-hydroxypiperidine (33.2 mg) and 1-hydroxybenzotriazole monohydrate (60 mg) in N,N-dimethylformamide (3 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg) and triethylamine (0.208 mL) at room temperature and the mixture was stirred overnight at room temperature. The mixture was partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was washed with saturated brine (30 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by basic silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→ethyl acetate:methanol=80:20), and crystallized from diisopropyl ether to give the title compound (168 mg).

Workup

  1. customThe mixture was partitioned between ethyl acetate (50 mL) and water (30 mL)
  2. washThe organic layer was washed with saturated brine (30 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was separated
  6. custompurified by basic silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→ethyl acetate:methanol=80:20)
  7. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-f5c89c3134d54b1383c277e40eb81b8c
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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