Triethylamine → HCID 35475094, compound

HRID 2369395Notes

Reaction equation

HRID 2369395 reaction equation
[CH2:1]([C:3]1[S:20][C:6]2[N:7]=[CH:8][N:9]=[C:10]([N:11]3[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=[O:18])[CH2:13][CH2:12]3)[C:5]=2[CH:4]=1)[CH3:2].N1(O)[C:25]2C=CC=C[C:24]=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.C(=O)(O)[O-].[NH4+]>CN(C)C=O.C(#N)C.O>[CH2:1]([C:3]1[S:20][C:6]2[N:7]=[CH:8][N:9]=[C:10]([N:11]3[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:24][CH3:25])=[O:18])[CH2:13][CH2:12]3)[C:5]=2[CH:4]=1)[CH3:2]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 14013Ammonium BicarbonateHCID 757711-HydroxybenzotriazoleHCID 1132958HCID 1132958, compoundHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 35475094HCID 35475094, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
30 °C

Procedure

A mixture of 1-[6-ethylthieno[2,3-d]pyrimidin-4-yl]piperidine-4-carboxylic acid (950 mg, 3.26 mmol, 1.00 equiv), 1H-1,2,3-benzotriazol-1-ol (586 mg, 4.34 mmol, 1.33 equiv), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (834 mg, 4.34 mmol, 1.33 equiv), amine hydrochloride (307 mg, 5.74 mmol, 1.76 equiv) and triethylamine (876 mg, 8.66 mmol, 2.66 equiv) in N,N-dimethylformamide (15 mL) was stirred for 12 h at 30° C. The reaction was then quenched by the addition of 30 mL of water. The resulting solution was extracted with 2×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×50 mL of brine. The resulting mixture was concentrated under vacuum. The crude product was purified by preparative HPLC (211-Waters 2767-2(HPLC-08)) under the following conditions: column: Xbridge Prep C,8, 5 um, 19*150 mm; mobile phase: water with 50 mmol ammonium bicarbonate and acetonitrile (10.0% acetonitrile up to 22.0% in 2 min, up to 32.0% in 10 min, up to 100.0% in 1 min, down to 10.0% in 1 min); detector: UV 220 nm. Purification afforded 167.4 mg (18%) of Compound I-177 as a white solid. 1H NMR: (400 MHz, CDCl3) δ 8.45 (1H, s), 6.95 (1H, s), 5.48-5.53 (1H, d), 4.54-4.57 (2H, d), 3.18-3.24 (2H, t), 2.89-2.92 (2H, q), 2.49-2.55 (1H, m), 2.03-2.05 (2H, m), 1.84-1.94 (2H, m), 1.35-1.38 (3H, t). MS: m/z 291 (M+H)+.

Workup

  1. customThe reaction was then quenched by the addition of 30 mL of water
  2. extractionThe resulting solution was extracted with 2×20 mL of ethyl acetate
  3. washThe resulting mixture was washed with 1×50 mL of brine
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. customThe crude product was purified by preparative HPLC (211-Waters 2767-2(HPLC-08)) under the following conditions
  6. waitup to 32.0% in 10 min
  7. waitup to 100.0% in 1 min
  8. waitdown to 10.0% in 1 min)
  9. customPurification

Sources & evidence

ORD record
ord-27896457a007478daacd7fc3eff80f8f
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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