Tris(hydroxymethyl)aminomethane → HCID 11221703, compound

HRID 1455607Notes

Reaction equation

HRID 1455607 reaction equation
N=C=N.[F:4][C:5]([F:24])([CH2:21][CH2:22][CH3:23])[CH2:6][CH:7]([NH:11][C:12]([N:14]1[CH2:20][CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:13])[C:8]([OH:10])=O.C1C=C[C:28]2[N:33](O)N=[N:31][C:29]=2C=1.Cl.NCC#N.C(O)C(N)(CO)CO>C(Cl)Cl.C(N(CC)CC)C>[C:29]([CH2:28][NH:33][C:8]([C@@H:7]([NH:11][C:12]([N:14]1[CH2:20][CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:13])[CH2:6][C:5]([F:4])([F:24])[CH2:21][CH2:22][CH3:23])=[O:10])#[N:31]

Participants

8

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 11491918Aminoacetonitrile hydrochlorideHCID 68821240HCID 68821240, compound

Product 1

HCID 11221703HCID 11221703, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A suspension of Polystyrene bound carbodiimide (570 mg, 0.73 mmol) and 4,4-Difluoro-2-[([1,4]oxazepane-4-carbonyl)-amino]-heptanoic acid (135 mg) in DCM (10 mL) stirred for 10 min. HOBT (60 mg) added, stirred for 10 min. A suspension of amino acetonitrile hydrochloride (34 mg) and triethyl amine (52 μL) in DCM (5 mL) added and stirred overnight at room temperature. PS-Trisamine (493 mg) added and stirred at room temperature for 2 h 30 min. After filtration, filtrate diluted with DCM, washed with water, evaporated under reduced pressure and purified by column chromatography eluting with ethyl acetate heptane mixture to give Perhydro-1,4-oxazepine-4-carboxylic acid [(S)-1-(cyanomethyl-carbamoyl)-3,3-difluoro-hexyl]-amide as a solid.

Workup

  1. stirringstirred for 10 min
  2. additionadded
  3. stirringstirred overnight at room temperature
  4. stirringstirred at room temperature for 2 h 30 min
  5. filtrationAfter filtration, filtrate
  6. additiondiluted with DCM
  7. washwashed with water
  8. customevaporated under reduced pressure
  9. custompurified by column chromatography
  10. washeluting with ethyl acetate heptane mixture

Sources & evidence

ORD record
ord-1eca230f9d1b40c7b1d805574a0d1d06
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

Loading…