Sodium triacetoxyborohydride → 2-[4-(5-Chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide

HRID 1922779Notes

Reaction equation

HRID 1922779 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH:11]=O)=[N:8][C:6]=2[N:7]=1.[N:19]1([C:25]([CH3:30])([CH3:29])[C:26]([NH2:28])=[O:27])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][N:22]3[CH2:21][CH2:20][N:19]([C:25]([CH3:30])([CH3:29])[C:26]([NH2:28])=[O:27])[CH2:24][CH2:23]3)=[N:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 217488412-Methyl-2-(piperazin-1-yl)propanamideHCID 576853925-Chloro-7-morpholinothiazolo[4,5-d]pyrimidine-2-carbaldehyde

Product 1

HCID 594182222-[4-(5-Chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramideYield 71%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 5-chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidine-2-carbaldehyde (250 mg, 0.88 mmol), 2-piperazin-1-yl-isobutyramide (173 mg, 1.01 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (15 mL) was stirred at RT under nitrogen atmosphere for 4 h. Sodium triacetoxyborohydride (280 mg, 1.32 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded on an Isolute® SCX-2 cartridge (25 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2 M NH3 in MeOH and DCM. The resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 6:94). The solvents were reduced in vacuo to afford the title compound as a yellow solid (275 mg, 60%). LCMS (Method H): RT 2.41 min, [M+H]+ 440. 1H NMR (400 MHz, CDCl3): δ 7.04 (1 H, br s), 5.22 (1 H, br s), 3.97-3.95 (6 H, m), 3.85 (4 H, t, J=4.80 Hz), 2.67 (8 H, m), 1.25 (6 H, s)

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at RT for 16 h
  3. washThe cartridge was washed with DCM/MeOH
  4. washthe desired product was subsequently eluted
  5. additiona mixture of 2 M NH3 in MeOH and DCM
  6. customThe resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 6:94)

Sources & evidence

ORD record
ord-3b3ade8b87de4cc486f78830dbd21fd6
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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