Dichloromethane → HCID 72484853, compound

HRID 1592776Notes

Reaction equation

HRID 1592776 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[CH:25]=[N:24][CH:23]=[N:22]2)[CH2:10][CH2:9]1)([O:3]C(C)(C)C)=O.[OH:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([CH3:38])([CH3:37])[NH:32][CH:31]([C:39]([OH:41])=O)[CH2:30]2.CCN([CH:48]([CH3:50])[CH3:49])C(C)C.[CH:51]1[CH:52]=[CH:53][C:54]2[N:59](O)N=NC=2[CH:56]=1.C(Cl)[Cl:62]>CN(C1C=CN=CC=1)C.C(Cl)CCl>[Cl:62][C:49]1[CH:48]=[CH:50][C:52]([CH2:53][CH:54]([NH:59][C:39]([CH:31]2[CH2:30][C:29]3[C:34](=[CH:35][CH:36]=[C:27]([OH:26])[CH:28]=3)[C:33]([CH3:37])([CH3:38])[NH:32]2)=[O:41])[C:1](=[O:3])[N:8]2[CH2:9][CH2:10][N:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:20][N:21]3[CH:25]=[N:24][CH:23]=[N:22]3)[CH2:12][CH2:13]2)=[CH:51][CH:56]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12197337HCID 12197337, compoundHCID 19969700HCID 19969700, compound

Product 1

HCID 72484853HCID 72484853, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Procedure

1-Boc-4-(2-[1,2,4]triazol-1-ylmethyl-phenyl)-piperazine was deprotected and coupled to Boc-D-p-Cl-Phe-OH in a manner similar to coupling procedure 1. The coupled product was deprotected and prepared as the chloride salt. To a solution of the chloride salt (1.16 g, 2.52 mmol), 6-hydroxy-1,1-dimethyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (714 mg), DIEA (1.75 mL), HOBt (408 mg), and DMAP (62 mg) in 2.52 mL of CH2Cl2 was added EDC (579 mg). After stirring overnight, the mixture was extracted with EtOAc, washed with water, saturated bicarbonate and brine, and then dried over Na2SO4, filtered and evaporated to dryness. The mixture was chromatographed with 5% MeOH/EtOAc. The diastereomers were separated on a waters symmetry C18 column 80:20 to 50:50 water (0.05% TFA) acetonitrile over 40 minutes detecting at 230 nm. LRMS (ESI+): 628.3 (M+1).

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. washwashed with water, saturated bicarbonate and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe mixture was chromatographed with 5% MeOH/EtOAc
  7. customThe diastereomers were separated on a waters symmetry C18 column 80:20 to 50:50 water (0.05% TFA) acetonitrile over 40 minutes

Sources & evidence

ORD record
ord-d6733bdc9abb4bdd8bd49aaaad59ec1b
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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