Diisopropylethylamine → HCID 20653482, compound

HRID 1976967Notes

Reaction equation

HRID 1976967 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15])=[O:7].[C:25]([NH:32][C@@H:33]([C:38](O)=[O:39])[CH2:34][CH:35]([CH3:37])[CH3:36])([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([NH:23][C:38](=[O:39])[C@H:33]([NH:32][C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:34][CH:35]([CH3:37])[CH3:36])=[CH:21][CH:22]=1)[NH:5][C:6](=[O:7])[C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 637604tert-Butoxycarbonyl-D-leucineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53816025HCID 53816025, compound

Product 1

HCID 20653482HCID 20653482, compoundYield 102%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-amino-N-[(2-chloro-6-methylphenyl)carbonyl]-L-phenylalanine methyl ester (561 mg, 1.61 mmol), prepared using procedure described in Example 68. in DMF (4.5 mL) was treated with N-Boc-D-leucine (393.2 mg, 1.7 mmol), HBTU (644.3 mg, 1.7 mmol) and DIPEA (0.62 mL, 3.50 mmol) at room temperature for 6 hr. The reaction mixture was diluted to 30 mL with water and the white precipitate was collected by filtration and was washed with water (2×2 mL). After drying under vacuum, the light yellow powder was recrystallized from ethyl acetate-hexane to give N-(2-chloro-6-methylbenzoyl)-4-[[(2R)-2-[(1,1dimethylethoxy)carbonyl]amino-4-methyl-1-oxopentyl]amino]-L-phenylalanine methyl ester (920 mg) as a white solid. MS 560 (M+H, 1 Cl). This solid was dissolved in 4 N HCl in dioxane (5 mL). The solution was stirred at room temperature overnight. After dilution with ether, the white suspension was allowed to stand at −5° C. for 1 hr. The white solid was collected by filtration and was dried under vacuum for 5 hr. The above solid was then dissolved in 20 mL of water and the solution was treated with sodium bicarbonate followed by K2CO3 to PH >9. The mixture was then extracted with dichloromethane (2×25 mL) and was dried over sodium sulfate. After removal of solvent, the residue was then dried under vacuum at 50° C. overnight to give white solid (520 mg, 1.1 mmol) in 70% overall yield. HRMS: Obs. 460.1997, Calc. 460.2003 (M+H).

Workup

  1. filtrationthe white precipitate was collected by filtration
  2. washwas washed with water (2×2 mL)
  3. customAfter drying under vacuum
  4. customthe light yellow powder was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-635e7f9d92064dd1b6252550d014bd86
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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