Tris(hydroxymethyl)aminomethane → Morpholine-4-carboxylic acid[(r)-2-cyclopropylmethanesulfonyl-1-(2,6-dihydroxy-cyclohexylcarbamoyl)-ethyl]-amide

HRID 460412Notes

Reaction equation

HRID 460412 reaction equation
[CH:1]1([CH2:4][S:5]([CH2:8][C@H:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[C:10]([OH:12])=O)(=[O:7])=[O:6])[CH2:3][CH2:2]1.C1(N=C=N)CCCCC1.OC1C2N=NNC=2C=CC=1.[NH2:41][CH:42]1[CH:47]([OH:48])[CH2:46][CH2:45][CH2:44][CH:43]1[OH:49].C(O)C(N)(CO)CO>C(Cl)Cl>[CH:1]1([CH2:4][S:5]([CH2:8][C@H:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[C:10](=[O:12])[NH:41][CH:42]2[CH:47]([OH:48])[CH2:46][CH2:45][CH2:44][CH:43]2[OH:49])(=[O:6])=[O:7])[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 3196702-Aminocyclohexane-1,3-diolHCID 12048208N-CyclohexylcarbodiimideHCID 60054540(R)-3-cyclopropylmethanesulfonyl-2-[(morpholine-4-carbonyl)-amino]-propionic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 86612925Morpholine-4-carboxylic acid[(r)-2-cyclopropylmethanesulfonyl-1-(2,6-dihydroxy-cyclohexylcarbamoyl)-ethyl]-amideYield 73.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-3-cyclopropylmethanesulfonyl-2-[(morpholine-4-carbonyl)-amino]-propionic acid (0.352 g, 1.1 mmol) and N-cyclohexylcarbodiimide N′-methylpolystyrene (1.93 mmol/g, 1.03 g) in DCM (10 mL) was treated with hydroxybenzotriazole (0.27 g, 2 mmol). After stirring at room temperature for 5 minutes the mixture was treated with 2-amino-cyclohexane-1,3-diol (0.0.13 g, 1 mmol) and stirring was continued for a further 2 days. The reaction mixture was treated with PS Trisamine (3.75 mmol/g, 1.3 g) and after stirring at room temperature for 2 hours the resin was filtered off and washed with DCM. The combined filtrate plus washings were evaporated under reduced pressure to give morpholine-4-carboxylic acid [(R)-2-cyclopropylmethanesulfonyl-1-(2,6-dihydroxy-cyclohexylcarbamoyl)-ethyl]-amide (0.32 g) as pale yellow thick oil. MS: 434 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued for a further 2 days
  3. stirringafter stirring at room temperature for 2 hours the resin
  4. filtrationwas filtered off
  5. washwashed with DCM
  6. customThe combined filtrate plus washings were evaporated under reduced pressure

Sources & evidence

ORD record
ord-fd952977479c4d6d99029df504a0af1b
Source dataset
uspto-grants-2007_03
Patent number
US07196099B2

Reaction notes

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