Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 69285726, compound

HRID 2225231Notes

Reaction equation

HRID 2225231 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH2:14])[C@H:10]([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)C.[F:29][C:30]([F:45])([F:44])[C:31]1[CH:32]=[C:33]([CH:41]=[CH:42][CH:43]=1)[C:34]([NH:36][CH2:37][C:38](O)=[O:39])=[O:35].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:38](=[O:39])[CH2:37][NH:36][C:34](=[O:35])[C:33]2[CH:41]=[CH:42][CH:43]=[C:31]([C:30]([F:29])([F:45])[F:44])[CH:32]=2)[C@H:10]([CH2:15][CH2:16][CH:17]([CH3:18])[CH3:19])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 521913N,N-Diethyl-2-propanamineHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 69285468HCID 69285468, compound

Product 1

HCID 69285726HCID 69285726, compoundYield 35.7%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A sample of [(1R,3R,4S)-4-amino-3-(3-methyl-butyl)-cyclohexyl]-carbamic acid tert-butyl ester (50 mg, 0.18 mmol) was dissolved in 1:1 CH2Cl2/DMF (2 mL). The resultant solution was charged successively with N,N-diethylisopropylamine (0.16 mL, 0.9 mmol), (3-trifluoromethyl-benzoylamino)-acetic acid (47 mg, 0.19 mmol, prepared as described in WO PCT 0250019), and BOP (116 mg, 0.26 mmol). The reaction was stirred for 12 h at RT and then partitioned between EtOAc and sat. NaHCO3; the aqueous phase was back extracted with EtOAc (1×). The organic phases were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography afforded {(1R, 3R,4S)-3-(3-methyl-butyl)-4-[2-(3-trifluoromethyl-benzoylamino)-acetylamino]-cyclohexyl}-carbamic acid tert-butyl ester (33 mg). MS found: (M+H)+=514.3.

Workup

  1. custompartitioned between EtOAc and sat. NaHCO3
  2. extractionthe aqueous phase was back extracted with EtOAc (1×)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-fb1a1896adbe4e60a27ce95c8fc40fd0
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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