Dichloromethane → 4-Cyclohexyl-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-benzamide

HRID 1174938Notes

Reaction equation

HRID 1174938 reaction equation
[CH3:1][N:2]([CH2:13][CH:14]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:6]=2[N:7]=1.[CH:20]1([C:26]2[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(Cl)Cl>C(Cl)Cl.CO>[CH:20]1([C:26]2[CH:27]=[CH:28][C:29]([C:30]([NH:12][C:9]3[CH:10]=[CH:11][C:5]4[O:4][C:3]([N:2]([CH3:1])[CH2:13][CH:14]5[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]5)=[N:7][C:6]=4[CH:8]=3)=[O:31])=[CH:33][CH:34]=2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 883374-Cyclohexylbenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 57771749Rac-n2-methyl-n2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine

Product 1

HCID 115974934-Cyclohexyl-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-benzamideYield 40%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Combine rac-N2-methyl-N2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine (0.150 g, 0.576 mmol), 4-cyclohexyl-benzoic acid (0.177 g, 0.864 mmol), HATU (0.219 g, 0.576 mmol), polystyrene-bound diisopropylamine (1.44 g, loading: 2.0 to 3.5 mmol/g), and CH2Cl2 (20 mL). Shake the mixture overnight at room temperature. Add HATU (0.219 g, 0.576 mmol) and shake for 21 h at room temperature. Dilute with 1:1 CH2Cl2/MeOH, wash with 10M NaOH (equal volume), dry over Na2SO4, filter, and concentrate in vacuo. Subject the mixture to silica gel flash column chromatography (2×12 g columns, 5% 2M NH3 in MeOH/CH2Cl2, then ramping to 10% after 10 min) to yield the desired product as a colorless oil (0.103 g, 40%). Subject the product to chiral preparative chromatography [Chiralpak AD-H column, (8×32 cm), eluting with 70/30 3 Å ethanol/ACN w/0.2% dimethylethylamine; Flow rate=350 mL/min] to yield isomer 1 (0.039 g). mass spectrum (m/e): 447.3 (M+1). 1H NMR (400 MHz, CDCl3): δ 7.83 (s, 1H), 7.80-7.76 (m, 2H), 7.48 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.6, 1.8 Hz, 1H), 7.31-7.27 (m, 2H), 7.20 (d, J=8.4 Hz, 1H), 3.61-3.46 (m, 2H), 3.19 (s, 3H), 2.77-2.51 (m, 6H), 2.42-2.37 (m, 1H), 2.37 (s, 3H), 2.07-1.97 (m, 1H), 1.91-1.80 (m, 4H), 1.76 (d, J=12.8 Hz, 1H), 1.61-1.52 (m, 1H), 1.48-1.22 (m, 4H).

Workup

  1. customthe mixture overnight
  2. customat room temperature
  3. washwash with 10M NaOH (equal volume)
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-38e19fc25c614f8fb080b5f9633c67c3
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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