Diisopropylethylamine → HCID 178522225, compound

HRID 1630295Notes

Reaction equation

HRID 1630295 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C@H:16]3[NH:21][CH2:20][CH2:19][N:18]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:17]3)=[O:15])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl.[NH:35]1[CH:39]=[C:38]([CH2:40][C:41](O)=[O:42])[N:37]=[CH:36]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH:35]1[CH:39]=[C:38]([CH2:40][C:41]([N:21]2[CH2:20][CH2:19][N:18]([C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:23])[CH2:17][C@H:16]2[C:14](=[O:15])[NH:13][C:10]2[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:32]=[CH:33][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:12][CH:11]=2)=[O:42])[N:37]=[CH:36]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56954161(S)-benzyl 3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylateHCID 178479752HCID 178479752, compound

Product 1

HCID 178522225HCID 178522225, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step (c) A flask was charged with (S)-benzyl 3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate (1.08 g, 2.41 mmol), 4-imidazoleacetic acid hydrochloride (392 mg, 2.41 mmol), DIEA (1.0 mL, 5.8 mmol), HATU (1.01 g, 2.65 mmol) and DMF (5 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 257, (S)-benzyl 4-(2-(1H-imidazol-4-yl)acetyl)-3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate (0.80 g, 1.43 mmol, 67% yield), as an off-white solid. 1H-NMR (400 MHz, CDCl3): 10.27 (s, 1H), 9.18 (s, 1H), 7.60-7.49 (m, 3H), 7.47-7.21 (m, 5H), 7.06-6.91 (m, 6H), 5.45 (s, 1H), 5.17 (s, 2H), 5.09-5.00 (m, 2H), 4.04 (m, 2H), 4.09-3.97 (m, 2H), 3.81-3.73 (m, 2H), 3.46-3.77 (m, 1H), 3.17 (dd J=13.6, 4.8 Hz, 1H), 3.13-3.00 (m, 1H). MS (EI) for C30H28FN5O5. found 558.2 (MH+).

Workup

  1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
  2. extractionThe mixture was extracted with ethyl acetate (20 mL)
  3. washthe extract was washed with deionized water (10 mL)
  4. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customProduct was purified from the residue by reverse phase HPLC

Sources & evidence

ORD record
ord-83a2de370aa949b5b76efe94b21e7da0
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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