p-Acetamidobenzoic acid → HCID 59784111, compound

HRID 2079766Notes

Reaction equation

HRID 2079766 reaction equation
[CH3:1][N:2]([C@@H:10]([CH3:39])[C:11]([NH:13][C@H:14]([C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C@H:21]1[C:26]([NH:28][C@H:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1)=[O:27])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].CCN(C(C)C)C(C)C.[C:49]([NH:52][C:53]1[CH:61]=[CH:60][C:56]([C:57](O)=[O:58])=[CH:55][CH:54]=1)(=[O:51])[CH3:50].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:49]([NH:52][C:53]1[CH:61]=[CH:60][C:56]([C:57]([N:23]2[CH2:24][CH2:25][N:20]([C:18]([C@@H:14]([NH:13][C:11](=[O:12])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:7])([CH3:8])[CH3:6])[CH3:39])[CH:15]([CH3:17])[CH3:16])=[O:19])[C@H:21]([C:26]([NH:28][C@H:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][CH2:31][CH2:30]3)=[O:27])[CH2:22]2)=[O:58])=[CH:55][CH:54]=1)(=[O:51])[CH3:50]

Participants

8

Reactant 5

HCID 19266p-Acetamidobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59784098HCID 59784098, compound

Product 1

HCID 59784111HCID 59784111, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Intermediate 7 (191 mg, 0.351 mmol) is dissolved in DMF (10 mL), to which is added DIEA (0.305 mL, 1.75 mmol). This mixture is stirred at room temperature for 0.5 h. 4-Acetamidobenzoic acid (66 mg, 0.368 mmol) is added, and stirring is continued for continued 1 h. HOBt (52 mg, 0.385 mmol) and HBTU (146 mg, 0.385 mmol) are then added and the entire mixture is stirred at room temperature for 2 h. The reaction mixture is diluted with EtOAc (100 mL) and washed sequentially with 1 M citric acid, brine, sat. NaHCO3, brine, water and brine. The EtOAc layer is then dried with MgSO4, filtered, and the solvent removed at room temperature under reduced pressure to afford a colorless gum. This material is purified by flash chromatography on silica gel (EtOAc) to give the title compound as a white foam (211 mg, 85% yield): 1H NMR δ (CDCl3) 6.40-7.62 (m, 11H), 4.25-5.30 (m, 5H), 3.93 (“br d”, 1H, Jobs=11.9 Hz), 3.47 (“br id”, 1H, Jobs=11.4, 3 Hz), 2.65-3.30 (br m, 7H), 1.70-2.22 (br m, 8H), 1.48 and 1.46 (s, 9H total), 1.28-1.34 (m, 3H), 0.60-1.12 (br m, 7H); LCMS (APCl+) 706.7 (MH+, 100%).

Workup

  1. stirringstirring
  2. waitis continued for continued 1 h
  3. stirringthe entire mixture is stirred at room temperature for 2 h
  4. washwashed sequentially with 1 M citric acid, brine, sat. NaHCO3, brine, water and brine
  5. dry with materialThe EtOAc layer is then dried with MgSO4
  6. filtrationfiltered
  7. customthe solvent removed at room temperature under reduced pressure
  8. customto afford a colorless gum
  9. customThis material is purified by flash chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-bba33b8037124f4789c84c5609147dd1
Source dataset
uspto-grants-2011_04
Patent number
US07932255B2

Reaction notes

Loading…