Carbodiimide → (S)-2-amino-4-hydroxy-N-(5-(3-(piperidin-4-yloxy)phenyl)pent-4-ynyl)butanamide

HRID 473513Notes

Reaction equation

HRID 473513 reaction equation
C([NH:8][C@H:9]([C:13]([OH:15])=O)[CH2:10][CH2:11][OH:12])(OC(C)(C)C)=O.C1C=C2N=NN(O)C2=CC=1.O.N=C=N.[NH2:30][CH2:31][CH2:32][CH2:33][C:34]#[C:35][C:36]1[CH:37]=[C:38]([CH:53]=[CH:54][CH:55]=1)[O:39][CH:40]1[CH2:45][CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][CH2:41]1.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>CN(C=O)C.C(Cl)Cl>[NH2:8][C@@H:9]([CH2:10][CH2:11][OH:12])[C:13]([NH:30][CH2:31][CH2:32][CH2:33][C:34]#[C:35][C:36]1[CH:55]=[CH:54][CH:53]=[C:38]([O:39][CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:37]=1)=[O:15]

Participants

8

Reactant 5

HCID 160435CarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 13066457(2S)-2-(((tert-butoxy)carbonyl)amino)-4-hydroxybutanoic acidHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 67203672Tert-butyl 4-(3-(5-aminopent-1-ynyl)phenoxy)piperidine-1-carboxylate

Product 1

HCID 52919591(S)-2-amino-4-hydroxy-N-(5-(3-(piperidin-4-yloxy)phenyl)pent-4-ynyl)butanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-Boc-L-Homoserine (16 mg, 0.075 mmol, 1.5 eq) and HOBT hydrate (12 mg, 0.085 mmol, 1.7 eq) in DMF (2 mL) was added PS-carbodiimide (also known as N-Cyclohexylcarbodiimide-N′-propoxymethyl polystyrene, purchased from Biotage) (80 mg, 1.25 mmol/g resin, 0.1 mmol, 2.0 eq). After 10 minutes, a solution of tert-butyl 4-(3-(5-aminopent-1-ynyl)phenoxy)piperidine-1-carboxylate (0.25 mL of a 0.2 M solution in DCM, 0.05 mmol, 1.0 eq) was added and the resulting solution stirred overnight. To the resulting solution was then added MP-carbonate resin (95 mg, 2.64 mmol/g resin, 0.25 mmols, 5 eq), the suspension stirred 2 hrs, filtered, the resin washed with DCM and the filtrate concentrated by rotovap. The residue was taken up in 20% TFA/DCM (2 mL) and stirred 1 hr, methanol (1 mL) was added, and the resulting solution concentrated by rotovap. The resulting residue was purified by HPLC to yield (S)-2-amino-4-hydroxy-N-(5-(3-(piperidin-4-yloxy)phenyl)pent-4-ynyl)butanamide as a gum. ESI-MS (m/z): Calculated for C20H29N3O3: 360.2 (M+1); Measured: 360.2.

Workup

  1. filtrationfiltered
  2. washthe resin washed with DCM
  3. concentrationthe filtrate concentrated by rotovap
  4. stirringstirred 1 hr
  5. additionmethanol (1 mL) was added
  6. concentrationthe resulting solution concentrated by rotovap
  7. customThe resulting residue was purified by HPLC

Sources & evidence

ORD record
ord-da90e28ef26449fbab292af5079c540e
Source dataset
uspto-grants-2014_01
Patent number
US08633322B2

Reaction notes

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