Triethylamine → HCID 69242001, compound

HRID 2242200Notes

Reaction equation

HRID 2242200 reaction equation
[S:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[C:31]([O:35][C:36]([N:38]1[CH2:42][C@@H:41]([CH2:43][NH2:44])[CH2:40][C@H:39]1[C:45]([N:47]1[CH2:51][CH2:50][S:49][CH2:48]1)=[O:46])=[O:37])([CH3:34])([CH3:33])[CH3:32].C(N(CC)CC)C>CN(C=O)C>[C:31]([O:35][C:36]([N:38]1[CH2:42][C@@H:41]([CH2:43][NH:44][C:6]([C:4]2[N:3]=[CH:2][S:1][CH:5]=2)=[O:8])[CH2:40][C@H:39]1[C:45]([N:47]1[CH2:51][CH2:50][S:49][CH2:48]1)=[O:46])=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 3042714-Thiazolecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69241294HCID 69241294, compound

Product 1

HCID 69242001HCID 69242001, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of thiazole-4-carboxylic acid (2.25 g, 17.6 mmol) and HOBt (2.60 g, 19.2 mmol) in anhydrous DMF (80 mL) at 0° C. was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (3.69 g, 19.2 mmol) followed by the dropwise addition of a solution of Example 17D (5.07 g, 16 mmol) in anhydrous DMF (50 mL) over 10 minutes, after which anhydrous triethylamine (4.45 mL, 32 mmol) was added to the mixture via syringe. The mixture was allowed to stir for 12 hours at room temperature, concentrated under reduced pressure and the residue was partitioned between ethyl acetate (100 mL) and H2O (30 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated to provide a yellow solid. The yellow solid was crystallized from ethyl acetate (30 mL). The white crystals were dried under vacuum at 40° C. for 12 hours to provide a white powder (4.8 g) as the titled compound. MS (ESI) m/e 427 (M+H)+, 425 (M−H)−; 1H NMR (500 MHz, CD3OD) δ ppm 1.41 (s, 5 H) 1.44 (s, 4 H), 1.66 (m, 1 H), 2.49 (m, 1 H), 2.59 (m, 1 H), 3.03 (m, 1 H), 3.13 (m, 1 H), 3.21 (m, 1 H), 3.48 (m, 2 H) 3.75 (m, 2 H) 3.85 (m, 1 H) 4.53 (m, 2 H) 4.66 (m, 1 H), 8.25 (s, 1 H), 8.99 (s, 1 H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customthe residue was partitioned between ethyl acetate (100 mL) and H2O (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide a yellow solid
  8. customThe yellow solid was crystallized from ethyl acetate (30 mL)
  9. customThe white crystals were dried under vacuum at 40° C. for 12 hours

Sources & evidence

ORD record
ord-7516418464e94b5a86fa19212bc9ec19
Source dataset
uspto-grants-2010_03
Patent number
US07671076B2

Reaction notes

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