1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Benzeneacetamide, alpha-(cyclopentylmethyl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-4-[(4-methyl-1-piperazinyl)sulfonyl]-, (alphaR)-

HRID 2353340Notes

Reaction equation

HRID 2353340 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl.[CH3:50][O:51][C:52]1[N:57]=[C:56]2[S:58][C:59]([NH2:61])=[N:60][C:55]2=[CH:54][CH:53]=1>C(Cl)Cl.CN(C=O)C.O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([NH:61][C:59]2[S:58][C:56]3[C:55]([N:60]=2)=[CH:54][CH:53]=[C:52]([O:51][CH3:50])[N:57]=3)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 28015575-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amineHCID 444754013-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid

Product 1

HCID 11432720Benzeneacetamide, alpha-(cyclopentylmethyl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-4-[(4-methyl-1-piperazinyl)sulfonyl]-, (alphaR)-

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of the title E compound, 3-cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid (5 g, 0.013 mol) in DCM (250 mL) is cooled to 0° C. and then charged HOBt hydrate (2.66 g, 0.019 mol), followed by EDCI hydrochloride (6 g, 0.031 mol). The reaction mixture is stirred at 0° C. for 5 h. After that the solution of the title F compound, 5-methoxy-thiazolo[5,4-b]pyridin-2-ylamine (2.36 g, 0.013 mol) and D1EA (8 mL, 0.046 mol) in a mixture of DCM (60 mL) and DMF (20 mL) is added dropwise over 30 min. Reaction temperature is maintained at 0° C. for 3 h, then at RT (28° C.) for 3 days. Reaction is diluted with (60 mL) of water and the organic layer is separated and washed with saturated sodium bicarbonate solution (2×50 mL) followed by water washing (2×50 mL) and saturated sodium chloride aqueous solution (1×150 mL). Finally the organic layer is dried over sodium sulfate, filtered, and evaporated under vacuo. The crude product is purified using column chromatography over silica gel (60-120 mesh), using 40% ethyl acetate in hexane as an eluent to afford 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide as a white solid: 1H NMR (400 MHz, CDCl3) δ 0.9-2.1 (m, 11H), 2.2 (s, 3H), 2.5 (br s, 4H), 3.1 (br s, 4H), 3.7 (m, 1H), 4.0 (s, 3H), 6.8 (d, J=8.8, 1H), 7.5 (d, J=8.3, 2H), 7.7 (d, J=8.3, 2H), 7.8 (d, J=8.8, 1H), 8.6 (s, 1H); MS 617 [M+1]+.

Workup

  1. additionis added dropwise over 30 min
  2. customReaction temperature
  3. temperatureis maintained at 0° C. for 3 h
  4. waitat RT (28° C.) for 3 days
  5. customReaction
  6. customthe organic layer is separated
  7. washwashed with saturated sodium bicarbonate solution (2×50 mL)
  8. dry with materialFinally the organic layer is dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated under vacuo
  11. customThe crude product is purified

Sources & evidence

ORD record
ord-7af3a7f9ed0749639728dfc15dafe7ae
Source dataset
uspto-grants-2010_07
Patent number
US07750020B2

Reaction notes

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