HCID 59606065, compound → HCID 59606106, compound

HRID 1922780Notes

Reaction equation

HRID 1922780 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][C:14](=[CH:17][C:18]2[S:19][C:20]3[N:21]=[C:22]([N:33]4[C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=5[N:35]=[C:34]4[CH2:42][CH3:43])[N:23]=[C:24]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[C:25]=3[N:26]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>CC(O)=O.[OH-].[OH-].[Pd+2]>[CH2:42]([C:34]1[N:33]([C:22]2[N:23]=[C:24]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[C:25]3[N:26]=[C:18]([CH2:17][CH:14]4[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]4)[S:19][C:20]=3[N:21]=2)[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=1)[CH3:43]

Participants

4

Reactant 1

HCID 59606065HCID 59606065, compound

Product 1

HCID 59606106HCID 59606106, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 4-[5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethylene]piperidine-1-carboxylic acid benzyl ester (300 mg, 0.50 mmol) in AcOH (20 mL) was added 10% Pd(OH)2/C (200 mg) and the resulting mixture stirred under an atmosphere of H2 for 2 h. The reaction mixture was filtered through Celite®, washing with EtOAc. The filtrate was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, 2M NH3/MeOH:DCM, 0-10%) affording 5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-yl-2-piperidin-4-ylmethylthiazolo[5,4-d]pyrimidine (96 mg, 41%). 1H NMR (CDCl3, 400 MHz): δ 7.99-7.98 (1 H, m), 7.74-7.73 (1 H, m), 7.30-7.26 (2 H, m), 4.43 (4 H, s), 3.88 (4 H, t, J=4.74 Hz), 3.33 (2 H, q, J=7.48 Hz), 3.12-3.08 (2 H, m), 2.99 (2 H, d, J=7.14 Hz), 2.63 (2 H, td, J=12.12, 2.54 Hz), 2.03-1.91 (1 H, m), 1.79 (2 H, brd d, J=13.18 Hz), 1.42 (3 H, t, J=7.48 Hz), 1.30-1.29 (2 H, m)

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. washwashing with EtOAc
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. customThe resulting residue was purified by column chromatography (Si—PCC, 2M NH3/MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-efad10051c2041679e35ac81b0c745ea
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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