Triethylamine → HCID 57791851, compound

HRID 1091717Notes

Reaction equation

HRID 1091717 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39](=[O:46])[NH:38][N:37]=2)=[CH:31][C:27]=1[C:28]([OH:30])=O.[F:47][CH2:48][CH:49]([O:52][CH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)[CH2:50][F:51].C(N(CC)CC)C>CN(C)C=O>[F:51][CH2:50][CH:49]([O:52][CH:53]1[CH2:54][CH2:55][N:56]([C:28]([C:27]2[CH:31]=[C:32]([CH:33]=[CH:34][C:26]=2[F:25])[CH2:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39](=[O:46])[NH:38][N:37]=2)=[O:30])[CH2:57][CH2:58]1)[CH2:48][F:47]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acidHCID 57791826HCID 57791826, compound

Product 1

HCID 57791851HCID 57791851, compoundYield 16.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (0.227 g, 0.60 mmol) was added in one portion to 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (0.137 g, 0.46 mmol), 4-(1,3-difluoropropan-2-yloxy)piperidine (28) (0.082 g, 0.46 mmol) and triethylamine (0.194 mL, 1.38 mmol) in N,N-dimethylformamide (3 mL) at 20° C. under air. The resulting solution was stirred at 20° C. for 24 hours. The crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired compound as a colourless gum (34 mg, 15.90%); 1H NMR (400.132 MHz, DMSO) δ 1.10-1.19 (1H, m), 1.21-1.30 (1H, m), 1.46-1.55 (2H, m), 1.62-1.70 (2H, m), 2.78-2.86 (1H, m), 3.54-3.60 (1H, m), 3.69-3.79 (2H, m), 4.11 (2H, s), 4.15-4.20 (1H, m), 4.22-4.32 (2H, m), 4.34-4.39 (1H, m), 6.97-7.02 (1H, m), 7.13-7.20 (2H, m), 7.59-7.69 (2H, m), 7.76 (1H, d), 8.05 (1H, d), 12.34 (1H, s); m/z (LC-MS, ESI+), RT=1.99 (M+H 460).

Workup

  1. customThe crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  2. additionFractions containing the desired compound
  3. customwere evaporated to dryness

Sources & evidence

ORD record
ord-03533ceb95424997b355cbdad53725f3
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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