4-Thiazoleacetic acid, 2-amino-, ethyl ester → HCID 57898961, compound

HRID 911046Notes

Reaction equation

HRID 911046 reaction equation
[C:1]1([O:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[S:20][CH:21]=[C:22]([CH2:24][C:25](OCC)=[O:26])[N:23]=3)[CH:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.ClC1C=C(OC2C3C(=CC=CC=3)C=CC=2)C=CN=1.NC1SC=C(CC(OCC)=O)N=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[C:1]1([O:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[S:20][CH:21]=[C:22]([CH2:24][CH2:25][OH:26])[N:23]=3)[CH:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 18520070HCID 18520070, compoundHCID 21226445Aluminium lithium hydrideHCID 86634765HCID 86634765, compound

Product 1

HCID 57898961HCID 57898961, compoundYield 37.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl 2-(2-(4-(naphthalen-1-yloxy)pyridin-2-ylamino)thiazol-4-yl)acetate (prepared from 2-chloro-4-(naphthalen-1-yloxy)pyridine (1.18 g, 4.61 mmol) and ethyl 2-(2-aminothiazol-4-yl)acetate according to the method of example 1 step B; 0.370 g, 0.913 mmol) in THF (4 ml) was added to a 1M solution of lithium aluminum hydride in THF (5 mL) at 0° C. The reaction mixture was stirred at ambient temperature for one hour, then cooled in an ice bath and quenched carefully with an excess of sodium sulfate decahydrate and stirred overnight. The reaction mixture was filtered, the solids were washed with THF several times, and the combined filtrate was concentrated. The crude material was purified via MPLC, eluting first with 1:1 hexane:ethyl acetate, followed by ethyl acetate. The component which eluted with ethyl acetate was concentrated and triturated with hexanes:dichloromethane (4:1, 15 mL), filtered, washed with hexanes, and dried to afford the title compound (0.125 g, 37.7% yield). 1H NMR (d6-DMSO) δ 2.67 (t, 2H), 3.63 (q, 2H), 4.57 (t, 1H), 6.51 (s, 1H), 6.57 (m, 214), 7.36 (d, 1H), 7.55-7.63 (m, 3H), 7.85 (d, 1H), 7.92 (d, 1H), 8.05 (d, 1H), 8.17 (d, 1H), 10.97 (s, 1H).

Workup

  1. temperaturecooled in an ice bath
  2. customquenched carefully with an excess of sodium sulfate decahydrate
  3. stirringstirred overnight
  4. filtrationThe reaction mixture was filtered
  5. washthe solids were washed with THF several times
  6. concentrationthe combined filtrate was concentrated
  7. customThe crude material was purified via MPLC
  8. washeluting first with 1:1 hexane
  9. washThe component which eluted with ethyl acetate
  10. concentrationwas concentrated
  11. customtriturated with hexanes:dichloromethane (4:1, 15 mL)
  12. filtrationfiltered
  13. washwashed with hexanes
  14. customdried

Sources & evidence

ORD record
ord-e08735dc80c44cd780a651aabb6b0c9e
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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