Benzylamine → HCID 71769707, compound

HRID 524128Notes

Reaction equation

HRID 524128 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:9][C:10]1[S:11][CH:12]=[C:13]([C:15](O)=[O:16])[N:14]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:1]([NH:8][C:15]([C:13]1[N:14]=[C:10]([Br:9])[S:11][CH:12]=1)=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 27632092-Bromo-1,3-thiazole-4-carboxylic acid

Product 1

HCID 71769707HCID 71769707, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Benzyl amine was loaded to 4-formyl-3,5-dimethoxyphenoxymethyl functionalized polystyrene resin (PAL) via reductive amination to give PAL-benzyl amine resin. See, Ding. S.; Grey, N. S. Wu, X.; Ding, Q.; Schultz, P. G. J. Am. Chem. Soc. 2002, 124, 1594-1596. A reaction flask containing PAL-benzyl amine resin (200 mg, 0.2 mmol), 2-bromothiazole-4-carboxylic acid (83 mg, 0.4 mmol), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) (153 mg, 0.6 mmol) and diisopropylethylamine (0.17 mL, 1 mmol) in DMF (3 mL) was shaken for 24 hr at room temperature. The resin was washed with methanol, dichloromethane and dried in vacuo to give PAL resin-N-benzyl-2-bromothiazole-4-carboxamide, which was then added to a flame-dried reaction vial, followed by 4-aminopyrimidine (95 mg, 1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), Xantphos (87 mg, 0.15 mmol) and NaOtBu (192 mg, 2 mmol). The vial was sure safe capped and degassed, then charged with argon and anhydrous dioxane (1.5 mL). The reaction was shaken for 24 hours at 90° C. The resin was washed with sodium diethyldithiocarbamate solution (0.05 M in DMF), methanol and dichloromethane and dried in vacuo. The resin was subsequently cleaved with cleavage cocktail TFA:CH2Cl2:H2O (45:55:5) (2 mL) for 2 hr. The resin was filtered, the filtrate was collected and evaporated in vacuo to give the crude which was then purified by HPLC to give the title compound (30 mg, 48%).

Workup

  1. washThe resin was washed with methanol, dichloromethane
  2. customdried in vacuo

Sources & evidence

ORD record
ord-819c9255bd974067bc11cbc93e2b5cbb
Source dataset
uspto-grants-2016_05
Patent number
US09340525B2

Reaction notes

Loading…