Dimethylformamide → HCID 69891310, compound

HRID 352712Notes

Reaction equation

HRID 352712 reaction equation
[CH3:1][CH:2]([CH3:33])[C@@H:3]([C:17]1[CH2:21][C:20](COC2C=CC=CC=2)([C:22](O)=[O:23])[O:19][N:18]=1)[NH:4][C:5]([C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=1)=[O:6].[C:34]([O:38][C:39](=[O:53])[CH2:40][C@H:41]([NH2:52])[CH:42]([OH:51])[CH2:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([CH3:37])([CH3:36])[CH3:35].[CH:54]1[CH:55]=[CH:56][C:57]2N(O)N=N[C:58]=2[CH:59]=1.C(N(CC)CC)C.CN([CH:74]=[O:75])C>C(Cl)CCl>[C:34]([O:38][C:39](=[O:53])[CH2:40][C@H:41]([N:52]([CH2:74][O:75][C:58]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:59]=1)[C:22]([CH:20]1[O:19][N:18]=[C:17]([C@@H:3]([NH:4][C:5]([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)=[O:6])[CH:2]([CH3:33])[CH3:1])[CH2:21]1)=[O:23])[C:42](=[O:51])[CH2:43][O:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 69838362HCID 69838362, compoundHCID 69891484HCID 69891484, compound

Product 1

HCID 69891310HCID 69891310, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

The title compound was prepared with conventional EDC coupling of 3-[2-methyl-(1S)-1-(naphthalene-2-carbonyl-amino)-propyl]-5-phenoxymethyl-4,5-dihydro-isoxazole-5-carboxylic acid (1.00 g, 2.24 mmol) and (3S)-3-amino-4-hydroxy-5-phenoxy-pentanoic acid t-butyl ester (630 mg, 1.0 eq), EDC (558 mg, 1.3 eq), HOBt (394 mg, 1.3 eq) and triethylamine (0.94 mL, 3.0 eq) in DMF (5 mL). Usual workup followed by flash chromatography gave 1.44 g of coupled product. The coupled product and Dess-Martin reagent (2.15 g, 2.5 mol eq) in dry CH2Cl2 (25 mL) under N2 at room temperature was stirred for 1 h, then quenched with isopropyl alcohol (3 mL). Usual extractive workup followed by flash chromatography (36% ethyl acetate-hexane) gave 1.27 g of the tide compound as diastereomeric mixture. Preparative HPLC (36% ethyl acetate-hexanes, 10 mL/min, 278 nm UV detection) afforded less polar (352 mg) and more polar (536 mg) diastereomers.

Sources & evidence

ORD record
ord-405f23a9a18b419d81bad8c3a3c52499
Source dataset
uspto-grants-2004_06
Patent number
US06747050B1

Reaction notes

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