4-Methylmorpholine → HCID 66735461, compound

HRID 2081132Notes

Reaction equation

HRID 2081132 reaction equation
CC(C)(C)[C@H](NC1C=CC=C(C(F)(F)F)C=1)C([N:6]1[CH2:11][C@H:10]2[C@H:8]([C:9]2([CH3:13])[CH3:12])[C@H:7]1[C:14]([OH:16])=O)=O.Cl[NH:31]C(CC1CCC1)C(=O)C(N)=O.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.OS([O-])(=O)=O.[K+]>CC#N>[CH3:13][C:9]1([CH3:12])[CH:8]2[CH:10]1[CH2:11][NH:6][CH:7]2[C:14]([NH2:31])=[O:16]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 516920Potassium bisulfateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57437887HCID 57437887, compoundHCID 57453595HCID 57453595, compound

Product 1

HCID 66735461HCID 66735461, compoundYield 110.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

(1R,2S,5S)-3-((S)-3,3-dimethyl-2-(3-(trifluoromethyl)phenylamino)butanoyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (0.043 g, 0.10 mmol), 3-(chloroamino)-4-cyclobutyl-2-oxobutanamide (0.031 g, 0.14 mmol), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDCI, 0.030 g, 0.16 mmol), 1-hydroxybenzotriazole hydrate (HOBt-H2O, 0.005 g, 0.03 mmol) in MeCN (3 mL) was added N-Methylmorpholine (d=0.920) (0.015 ml, 0.14 mmol) in MeCN (1 mL) dropwise over 40 minutes. The mixture was stirred at rt for 2 hrs and saturated KHSO4 (3 mL) was added, extracted with EtOAc (2×10 mL). The combined EtOAc extracts was washed with brine (10 mL), dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Hexane:Ethyl acetate=1:1) to give the (1R,2S,5S)—N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-3,3-dimethyl-2-(3-trifluoromethyl)phenylamino)butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide (0.017 g, 29%) as white solid. MS: Calcd.: 564; Found: [M+H]+ 565. 1H NMR (400 MHz, d6-DMSO) δ 8.23 (m, 1H), 7.96 & 7.89 (s, 1H), 7.71 & 7.67 (s, 1H), 7.17 (m, 1H), 7.06 (s, 1H), 6.92 (m, 1H), 6.76 (m, 1H), 5.67 (d, J=10.8 Hz, 1H), 4.93 & 4.75 (m, 1H), 4.17 (s, 1H), 3.99 (m, 1H), 3.82 (m, 1H), 3.68 (m, 1H), 2.29 (m, 1H), 1.91 (m, 2H), 1.70 (m, 3H), 1.58 (m, 2H), 1.43 (m, 1H), 1.20 (m, 1H), 0.92-1.00 (m, 14H), 0.61 (s, 1H), 0.57 (s, 1H).

Workup

  1. extractionextracted with EtOAc (2×10 mL)
  2. washThe combined EtOAc extracts was washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of solvent
  5. customthe residue was purified by chromatography (Hexane:Ethyl acetate=1:1)

Sources & evidence

ORD record
ord-a9802cfc8a3640009b6ac9a39b378f66
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

Loading…