Tris(hydroxymethyl)aminomethane → Morpholine-4-carboxylic acid (2-cyclopropylmethanesulfonyl-1-{1-[hydroxy-(5-phenyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide

HRID 489639Notes

Reaction equation

HRID 489639 reaction equation
C1(C2N=C(C(C(N[C:15]([CH:17]([NH:26][C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:18][S:19]([CH2:22][CH:23]([CH3:25])[CH3:24])(=[O:21])=[O:20])=[O:16])CC)=O)ON=2)CC1.C1(N=C=N)CCCCC1.C1C=CC2N(O)N=NC=2C=1.[NH2:54][CH:55]([CH2:69][CH3:70])[C@@H:56]([C:58]1[N:62]=[C:61]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[O:60][N:59]=1)[OH:57].C(O)C(N)(CO)CO>C(Cl)Cl>[CH:23]1([CH2:22][S:19]([CH2:18][CH:17]([NH:26][C:27]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)=[O:28])[C:15](=[O:16])[NH:54][CH:55]([CH:56]([OH:57])[C:58]2[N:62]=[C:61]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[O:60][N:59]=2)[CH2:69][CH3:70])(=[O:20])=[O:21])[CH2:24][CH2:25]1

Participants

7

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 757711-HydroxybenzotriazoleHCID 10239165Morpholine-4-carboxylic acid [1-[1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-2-(2-methyl-propane-1-sulfonyl)-ethyl]-amideHCID 12048208N-CyclohexylcarbodiimideHCID 67301524(S)-2-Amino-1-(5-phenyl-1,2,4-oxadiazol-3-yl)-butan-1-ol

Product 1

HCID 86590022Morpholine-4-carboxylic acid (2-cyclopropylmethanesulfonyl-1-{1-[hydroxy-(5-phenyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amideYield 109.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (R)-3-cyclopropylmethanesulfonyl-2-[(morpholine-4-carbonyl)-amino]-propionic acid (110 mg, 0.344 mmol, Reference Example 4) in methylene chloride (10 mL) was treated with PS-bound N-cyclohexylcarbodiimide (HL 200-400 mesh cross linked with 2% DVB) from Novabiochem (320 mg, 0.618 mmol, 1.93 mmol/g loading) and stirred at room temperature for 10 minutes. HOBt (43 mg, 0.319 mmol) was added followed by (S)-2-amino-1-(5-phenyl-1,2,4-oxadiazol-3-yl)-butan-1-ol (73 mg, 0.313 mmol, Reference Example 12) and the reaction mixture was stirred at room temperature overnight. PS-trisamine from Argonaut Technologies (413 mg, 1.549 mmol, 3.75 mmol/g loading) was added and the reaction was stirred for another 3 hours. The mixture was filtered and the filtrate was evaporated under reduced pressure to give morpholine-4-carboxylic acid (2-cyclopropylmethanesulfonyl-1-{1-[hydroxy-(5-phenyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide as an orange solid (183 mg). MS: 536 (MH+)

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. stirringthe reaction was stirred for another 3 hours
  3. filtrationThe mixture was filtered
  4. customthe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-78688f5395144f19830c2592a16515b0
Source dataset
uspto-grants-2005_12
Patent number
US06977256B2

Reaction notes

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