4-Methylmorpholine → HCID 59363853, compound

HRID 1430619Notes

Reaction equation

HRID 1430619 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:3]=1[O:4][C:5]([CH3:11])([CH2:9][CH3:10])[C:6]([OH:8])=O.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[CH2:34]([O:36][C:37](=[O:45])[CH2:38][C:39]1[N:40]=[C:41]([NH2:44])[S:42][CH:43]=1)[CH3:35].CCN=C=NCCCN(C)C>C(Cl)Cl>[CH2:34]([O:36][C:37](=[O:45])[CH2:38][C:39]1[N:40]=[C:41]([NH:44][C:6](=[O:8])[C:5]([O:4][C:3]2[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:2]=2[F:1])([CH3:11])[CH2:9][CH3:10])[S:42][CH:43]=1)[CH3:35]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 67486533HCID 67486533, compound

Product 1

HCID 59363853HCID 59363853, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2,4-Difluoro-phenoxy)-2-methyl-butyric acid (0.2 g, 0.87 mmol) in DCM (5 ml) added N-Methyl morpholine (0.6 ml, 5.2 mmol) and HOBt (0.2 g, 1.3 mmol) at 0° C. After stirring at this temperature for 5 min. added (2-Amino-thiazol-4-yl)-acetic acid ethyl ester (0.17 g, 0.92 mmol) and followed by EDCI (0.217 g, 1.3 mmol). The resulting solution was stirred for 12 h. then quenched with sat NH4Cl solution (15 ml). The aqueous phase was extracted with CH2Cl2 (3×50 ml). The organic phase were successively washed with 2% HCl (50 ml), brine (50 ml) and dried over Na2SO4. After evaporation, the residue was purified by flash chromatography to give {2-[2-(2,4-Difluoro-phenoxy)-2-methyl-butyrylamino]-thiazol-4-yl}-acetic acid ethyl ester (0.2 g, 59%). 1H NMR (400 MHz, CDCl3): 1.03 (t, J=7.2 Hz, 3H), 1.28 (t, J=7.6 Hz, 3H), 1.43 (s, 3H), 1.83-1.89 (m, 1H), 2.04-2.1 (m, 1H), 3.73 (s, 2H), 4.2 (q, J=6.8 Hz, 2H), 6.8-6.93 (m, 3H), 7.0-7.04 (m, 1H); MS (EI) m/z: 399 (M+1).

Workup

  1. stirringThe resulting solution was stirred for 12 h.
  2. customthen quenched with sat NH4Cl solution (15 ml)
  3. extractionThe aqueous phase was extracted with CH2Cl2 (3×50 ml)
  4. washThe organic phase were successively washed with 2% HCl (50 ml), brine (50 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter evaporation
  7. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-f2e3dca6aa02482e9cab241ad5bbe003
Source dataset
uspto-grants-2015_01
Patent number
US08940900B2

Reaction notes

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