Methyl N-(triethylammoniosulfonyl)carbamate → N-(3-methyl-5-{2-[2-(1,3,4-oxadiazol-2-yl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

HRID 1040105Notes

Reaction equation

HRID 1040105 reaction equation
[CH:1]([NH:3][NH:4][C:5](=O)[C:6]([CH3:31])([C:8]1[S:9][C:10]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:16]=[C:15]([CH3:30])[CH:14]=2)=[CH:11][N:12]=1)[CH3:7])=[O:2].CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH3:30][C:15]1[CH:16]=[C:17]([NH:19][C:20]2[N:25]=[C:24]([C:26]([F:27])([F:29])[F:28])[CH:23]=[CH:22][N:21]=2)[CH:18]=[C:13]([C:10]2[S:9][C:8]([C:6]([C:5]3[O:2][CH:1]=[N:3][N:4]=3)([CH3:31])[CH3:7])=[N:12][CH:11]=2)[CH:14]=1

Participants

4

Reactant 2

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 67431912N'-formyl-2-methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanehydrazide

Product 1

HCID 58456237N-(3-methyl-5-{2-[2-(1,3,4-oxadiazol-2-yl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amineYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product from Step 2 (80 mg, 0.172 mmol) was taken up in THF (2 mL) in a microwave vial, and Burgess reagent (82 mg, 0.344 mmol) was added. The reaction was irradiated in the microwave at 100° C. for 30 min. The yellow reaction mixture was concentrated to dryness, and the resulting residue was purified by column chromatography on silica (0-100% ethyl acetate in hexanes) to provide N-(3-methyl-5-{2-[2-(1,3,4-oxadiazol-2-yl)propan-2-yl]-1,3-thiazol-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine (32 mg, 42%) as an off-white solid. MS ESI: [M+H]+ m/z 447.0. 1H NMR (600 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.20 (s, 1H), 8.81 (d, J=4.9, 1H), 7.97 (s, 2H), 7.44 (s, 1H), 7.26 (d, J=4.9, 1H), 7.14 (s, 1H), 2.29 (s, 3H), 1.87 (s, 6H). rhSYK activity=+++

Workup

  1. additionwas added
  2. customThe reaction was irradiated in the microwave at 100° C. for 30 min
  3. concentrationThe yellow reaction mixture was concentrated to dryness
  4. customthe resulting residue was purified by column chromatography on silica (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-482f0f70f21d42c59d44b337e61c7fb9
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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