1,2-Dichloroethane → HCID 59547322, compound

HRID 2038558Notes

Reaction equation

HRID 2038558 reaction equation
[NH2:1][C@@H:2]([CH2:11][CH2:12][CH3:13])[CH:3]([OH:10])[C:4]([NH:6][CH:7]1[CH2:9][CH2:8]1)=[O:5].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH:28]1([CH2:34][C:35]([NH:37][C@@H:38]([C:60]([CH3:63])([CH3:62])[CH3:61])[C:39]([N:41]2[C@H:56]([C:57](O)=[O:58])[CH2:55][C@:43]3([O:47][C:46](=[O:48])[N:45]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[CH2:44]3)[CH2:42]2)=[O:40])=[O:36])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C.NCCC1N=CNC=1>CN(C=O)C.C(OCC)(=O)C>[CH:28]1([CH2:34][C:35]([NH:37][C@@H:38]([C:60]([CH3:63])([CH3:62])[CH3:61])[C:39]([N:41]2[C@H:56]([C:57]([NH:1][C@@H:2]([CH2:11][CH2:12][CH3:13])[CH:3]([OH:10])[C:4]([NH:6][CH:7]3[CH2:8][CH2:9]3)=[O:5])=[O:58])[CH2:55][C@:43]3([O:47][C:46](=[O:48])[N:45]([C:49]4[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=4)[CH2:44]3)[CH2:42]2)=[O:40])=[O:36])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 23634853(3S)-3-Amino-N-cyclopropyl-2-hydroxyhexanamideHCID 59547282HCID 59547282, compoundHCID 178419017HCID 178419017, compound

Product 1

HCID 59547322HCID 59547322, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide (20 mg, 87 μmol, 1.4 eq.), EDC (17 mg, 87 μmol, 1.4 eq.) and HOBt (13 mg, 87 μmol, 1.4 eq.) were combined in DMF (0.3 mL) and stirred at room temp. for 0.5 hrs. (5S,8S)-7-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-2-oxo-3-phenyl-1-oxa-3,7-diazaspiro[4.4]nonane-8-carboxylic acid (H1) (31 mg 62 μmol, 1 eq.) and DIEA (33 μL, 186 mol, 3 eq.) were added to the mixture and stirred at room temp. overnight. 1.0 M histamine (aq., 31 μL, 0.5 eq.) was added and the resulting mixture was stirred for 0.5 hrs. Ethyl acetate was added and the mixture was washed first with 1N HCl then with 1M K2CO3; and then extracted with ethyl acetate. The combined organic layers concentrated and chromatography using DCM and 20% MeOH in DCM gave 20 mg (30 μmol) of (5S,8S)-7-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)-2-oxo-3-phenyl-1-oxa-3,7-diazaspiro[4.4]nonane-8-carboxamide (I1). LC MS+/−: 668.56/666.64 at 3.24 min (10-90%, 3-5 min, Formic Acid).

Workup

  1. stirringstirred at room temp. overnight
  2. stirringthe resulting mixture was stirred for 0.5 hrs
  3. washthe mixture was washed first with 1N HCl
  4. extractionand then extracted with ethyl acetate
  5. concentrationThe combined organic layers concentrated

Sources & evidence

ORD record
ord-9855319175824964aade70386834b0e5
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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