Triethylamine → HCID 178424682, compound

HRID 1488105Notes

Reaction equation

HRID 1488105 reaction equation
[C:1]([CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=2)[C:15]([OH:17])=O)=[C:7]([CH3:9])[N:8]=1)#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:46][C:47]1([C:51]2[CH:58]=[CH:57][C:54]([C:55]#[N:56])=[CH:53][CH:52]=2)[CH2:50][NH:49][CH2:48]1.C(N(CC)CC)C>CN(C)C=O.C(#N)C.O>[C:1]([CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=2)[C:15]([N:49]2[CH2:48][C:47]([C:51]3[CH:52]=[CH:53][C:54]([C:55]#[N:56])=[CH:57][CH:58]=3)([F:46])[CH2:50]2)=[O:17])=[C:7]([CH3:9])[N:8]=1)#[N:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 900213344-(3-Fluoroazetidin-3-yl)benzonitrile hydrochloride2×HCID 178424683HCID 178424683, compound2×

Product 1

HCID 178424682HCID 178424682, compoundYield 15.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

Into a 100-mL round-bottom flask, was placed a solution of 5-(2-(cyanomethyl)-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 222.6, 190 mg, 0.71 mmol) and HBTU (538 mg, 1.42 mmol) in NA-dimethylformamide (3 mL). To the above were added a solution of 4-(3-fluoroazetidin-3-yl)benzonitrile hydrochloride (compound 43.4, 160 mg, 0.75 mmol) and triethylamine (197 μL, 1.42 mmol) in N,N-dimethylformamide (3 mL) dropwise. The reaction mixture was stirred for 1 h at room temperature. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, XBridge Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, Water with 50 mmol NH4HCO3 and acetonitrile (30% acetonitrile up to 44% in 7 min, hold 44% in 1 min, up to 100% in 1 min, down to 30% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 45.9 mg (15%) of the title compound as a white solid. m/z (ES+) 428 (M+H)+.

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. customThe crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  3. customin 1 min
  4. waitup to 100% in 1 min
  5. waitdown to 30% in 1 min)

Sources & evidence

ORD record
ord-63b9825fcf6e484cae3b54cf239b2558
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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