Sodium triacetoxyborohydride → 5-Chloro-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[4,5-d]pyrimidine

HRID 1922777Notes

Reaction equation

HRID 1922777 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.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[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:19]3[CH2:22][CH:21]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH2:20]3)=[N:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 134019734-(Azetidin-3-yl)morpholineHCID 576853925-Chloro-7-morpholinothiazolo[4,5-d]pyrimidine-2-carbaldehyde

Product 1

HCID 596060455-Chloro-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[4,5-d]pyrimidineYield 46%

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), 4-azetidin-3-yl-morpholine (150 mg, 1.05 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (15 mL) was stirred at RT under nitrogen atmosphere for 1.5 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 (10 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: 0:100 to 6:94 by volume). The solvents were reduced in vacuo to afford the title compound as a yellow solid (165 mg, 46%). LCMS (Method A): RT 2.31 min, [M+H]+ 411. 1H NMR (400 MHz, CDCl3): δ 4.11 (2 H, s), 3.95 (4 H, t, J=4.85 Hz), 3.83 (4 H, t, J=4.84 Hz), 3.74-3.67 (6 H, m), 3.22 (2 H, t, J=6.84 Hz), 3.12-3.11 (1 H, m), 2.34 (4 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 2M NH3 in MeOH and DCM
  6. customThe resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: 0:100 to 6:94 by volume)

Sources & evidence

ORD record
ord-5a45ae5154914800943d93b9a6463168
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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