Dichloromethane → HCID 18601570, compound

HRID 1589315Notes

Reaction equation

HRID 1589315 reaction equation
[CH3:1][NH:2][C:3](=[O:24])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[CH:16][CH:15]=1)[NH:5]C(OC(C)(C)C)=O.FC(F)(F)C(O)=O.[Cl:32]CCl>>[ClH:32].[CH3:1][NH:2][C:3](=[O:24])[C@H:4]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[CH:18][CH:19]=1)[NH2:5]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 18601567HCID 18601567, compound

Product 1

HCID 18601570HCID 18601570, compound

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. customThe solvent was removed in vacuo
  2. dissolutionthe residue redissolved in ether saturated with hydrogen chloride

Sources & evidence

ORD record
ord-92408155bea24e19bb83fff1e9aacce3
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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