Triethylamine → HCID 178494659, compound

HRID 1487834Notes

Reaction equation

HRID 1487834 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]([CH2:19][O:20][CH3:21])[NH:7][C:8]=2[C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[CH3:18])[C:12](O)=[O:13])[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:47]1[CH2:52][CH2:51][CH:50]([C:53]2[CH:60]=[CH:59][C:56]([C:57]#[N:58])=[CH:55][CH:54]=2)[CH2:49][CH2:48]1.C(N(CC)CC)C>ClCCl>[CH:1]1([C:4]2[N:5]=[C:6]([CH2:19][O:20][CH3:21])[NH:7][C:8]=2[C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[CH3:18])[C:12]([N:47]2[CH2:52][CH2:51][CH:50]([C:53]3[CH:60]=[CH:59][C:56]([C:57]#[N:58])=[CH:55][CH:54]=3)[CH2:49][CH2:48]2)=[O:13])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178494660HCID 178494660, compound2×

Product 1

HCID 178494659HCID 178494659, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a round-bottom flask, was placed a solution of 3-(4-cyclopropyl-2-(methoxymethyl)-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 4.10, 30 mg, 0.10 mmol) in dichloromethane (5 mL). HBTU (76 mg, 0.20 mmol), 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.2, 35 mg, 0.15 mmol, 1.50 equiv) and triethylamine (28 μL, 0.20 mmol) were added and the mixture was stirred overnight at room temperature. The mixture was diluted with DCM (30 mL) and washed with water (3×15 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (25.0% CH3CN up to 38.0% in 7 min, up to 100.0% in 3 min, down to 25.0% in 1 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing pure compound were combined and lyophilized to yield the title compound as a white solid (5.9 mg, 12%). m/z (ES+) 455 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J=8.0 Hz, 2H), 7.59-7.53 (m, 2H), 7.53-7.47 (m, 3H), ˜4.9-4.75 (m, 1H partially obscured by water peak), 4.72 (s, 2H), 3.99-3.85 (m, 1H), 3.52 (s, 3H), ˜3.3 (m, 1H overlapped with methanol solvent peak), 3.08-2.93 (m, 2H), 2.37 (s, 3H), 2.08-1.93 (m, 1H), 1.93-1.65 (m, 4H), 1.02-0.94 (m, 2H), 0.74-0.68 (m, 2H).

Workup

  1. customInto a round-bottom flask, was placed
  2. washwashed with water (3×15 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  7. waitmobile phase, water with 0.05% TFA and CH3CN (25.0% CH3CN up to 38.0% in 7 min
  8. waitup to 100.0% in 3 min
  9. waitdown to 25.0% in 1 min)
  10. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-838bf283a55640558d939977051cdbd6
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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