1,2-Dichloroethane → HCID 11576336, compound

HRID 2375436Notes

Reaction equation

HRID 2375436 reaction equation
[CH3:1][C:2]([CH3:20])([CH2:18][CH3:19])[CH2:3][CH2:4][C@H:5]([NH:9][C:10]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[O:11])[C:6]([OH:8])=O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:35][C:36]1([C:47]#[N:48])[CH2:41][CH2:40][N:39]([CH2:42][CH2:43][CH2:44][O:45][CH3:46])[CH2:38][CH2:37]1>ClCCl>[C:47]([C:36]1([NH:35][C:6]([C@@H:5]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[O:11])[CH2:4][CH2:3][C:2]([CH3:1])([CH3:20])[CH2:18][CH3:19])=[O:8])[CH2:41][CH2:40][N:39]([CH2:42][CH2:43][CH2:44][O:45][CH3:46])[CH2:38][CH2:37]1)#[N:48]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 45113625HCID 45113625, compoundHCID 59854953HCID 59854953, compound

Product 1

HCID 11576336HCID 11576336, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (S)-5,5-Dimethyl-2-[(morpholine-4-carbonyl)-amino]-heptanoic acid (4.70 g, 16.4 mmol) in dichloromethane (75 mL), cooled in an ice water bath, was treated with HOBT (2.45 g, 18.13 mmol), then EDC (3.47 g, 18.1 mmol). The reaction mixture was stirred with cooling for 35 min, then the ice bath was removed and a solution of 4-amino-(3-methoxy-propyl)-piperidine-4-carbonitrile (3.61 g, 18.3 mmol) in dichloromethane (25 mL) was added. The reaction mixture was stirred overnight, then concentrated on a rotary evaporator. The resulting residue was taken up in ethyl acetate (300 mL) and washed with saturated sodium bicarbonate solution (2×300 mL). The organic phase was then dried (magnesium sulfate) and concentrated to provide 8.1 grams of crude material. This material was further purified on a shimadzu reverse phase hplc using a gradient of acetonitrile in water (40 to 65% over 35 min flow rate 45 mL/min) to provide 1.18 g (25.8%) of the desired product as a white crunchy foam; m/z calculated for C24H43N5O4 465.6, found 466.6 (M+H)+

Workup

  1. temperaturewith cooling for 35 min
  2. customthe ice bath was removed
  3. stirringThe reaction mixture was stirred overnight
  4. concentrationconcentrated on a rotary evaporator
  5. washwashed with saturated sodium bicarbonate solution (2×300 mL)
  6. dry with materialThe organic phase was then dried (magnesium sulfate)
  7. concentrationconcentrated
  8. customto provide 8.1 grams of crude material
  9. customThis material was further purified on a shimadzu reverse phase
  10. customa gradient of acetonitrile in water (40 to 65% over 35 min flow rate 45 mL/min)

Sources & evidence

ORD record
ord-af9f694a9dc0482699e9d12643c560ef
Source dataset
uspto-grants-2008_12
Patent number
US07465745B2

Reaction notes

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