4-Methylmorpholine → HCID 86740655, compound

HRID 1589316Notes

Reaction equation

HRID 1589316 reaction equation
[CH2:1]([NH:7][C:8](=[O:29])[C@H:9]([CH:26]([CH3:28])C)[NH:10][C:11](=[O:25])[C@H:12]([CH2:21][CH:22]([CH3:24])[CH3:23])[NH:13]C(OC(C)(C)C)=O)CCCCC.ON1C2C=CC=CC=2N=N1.Cl.CNC(=O)[C@H](CC1[CH:52]=[CH:51][C:50]([O:53][CH2:54][CH2:55][CH3:56])=[CH:49][CH:48]=1)N.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C=O>[CH3:1][NH:7][C:8](=[O:29])[C@H:9]([CH2:26][C:28]1[CH:52]=[CH:51][C:50]([O:53][CH2:54][CH2:55][CH3:56])=[CH:49][CH:48]=1)[NH:10][C:11](=[O:25])[C@H:12]([CH2:21][CH:22]([CH3:23])[CH3:24])[NH2:13]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18597344HCID 18597344, compoundHCID 18601570HCID 18601570, compound

Product 1

HCID 86740655HCID 86740655, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

N-Tertiary butyloxycarbonyl-O-propyl-L-tyrosine N-methyl amide (370 mg, 1.1 mM) in dichloromethane (8 ml) was treated with trifluoroacetic acid (2 ml) at 20° C. for 2 h. The solvent was removed in vacuo and the residue redissolved in ether saturated with hydrogen chloride and this procedure repeated twice more to afford O-propyl-L-tyrosine-N-methyl amide hydrochloride (1.1 mM) which was used directly in the next step. N-(3-N-(Benzyloxycarbonyl)amino-1-(R)-methoxycarbonylpropyl)-L-leucine hydrochloride (prepared as described in Example 1) (416 mg, 1 mM) in dichloromethane (10 ml) and dimethyl formamide (2 ml) was treated with 1-hydroxybenzotriazole (159 mg, 1.04 mM), O-propyl-L-tyrosine-N-methyl amide hydrochloride (1.1 mM), N-methyl morpholine (315 mg, 3.3 mM) and N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (200 mg, 1.04 mM) at 0° C. The reaction mixture was stirred continuously as it was allowed to warm to 20° C. over 16 h. The reaction was diluted with dichloromethane (30 ml) and washed successively with water, aqueous saturated sodium hydrogen carbonate and aqueous citric acid (1M) dried over anhydrous sodium sulphate and concentrated in vacuo to afford N-(3-N-Benzyloxycarbonyl)amino-1-(R)-methoxycarbonylpropyl)-L-leucyl-O-propyl-L-tyrosine-N-methyl amide (0.22 g, 0.36 mM) which crystallised from ethyl acetate/hexane as needles m.p. 135°-140° C. (Found: C,62.8; H,7.8; N,9.2. C32H46N4O7 +0.5 H2O requires: C,63.2; H,7.8; N,9.2%); δ(CDCl3) 0.86 (6H,d,d,J=4 Hz J=4 Hz (CH3)2C); 1.02 (3H,t,J=7 Hz CH3CH2); 1.1-1.98 (9H,m,CH,CH2,CH2,CH2CH2); 2.74 (3H,d,J=4 Hz CH3NH); 2.86-3.48, (5H,m,CH2CH2,CH); 3.64 (3H,s,OCH3); 3.86 (2H,t,J=6 Hz,CH2O); 4.58 (1H,m,NHCHCO); 5.06 (2H,s,CH2C6H5); 5.14 (1H,m,NH) 6.54 (1H,m,NH); 6.76, and 7.06 (4 H,each d, each J=8 Hz,C6H4); 7.32 (5H,m,C6H5); 7.42 (1H,m,NH).

Workup

  1. washwashed successively with water, aqueous saturated sodium hydrogen carbonate and aqueous citric acid (1M)
  2. dry with materialdried over anhydrous sodium sulphate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f213b86671954c1a816ca8829a996c47
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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