4-Methylmorpholine → HCID 67114148, compound

HRID 41918Notes

Reaction equation

HRID 41918 reaction equation
[CH:1]1([CH:7]([NH:30][C:31]([C:33]2[CH:38]=[N:37][CH:36]=[CH:35][N:34]=2)=[O:32])[C:8]([NH:10][CH:11]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:12]([N:14]2[CH:22]3[CH:17]([CH2:18][CH2:19][CH2:20][CH2:21]3)[CH2:16][CH:15]2[C:23](O)=[O:24])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Cl.[CH2:80]([O:82][C:83](=[O:91])[CH:84]([OH:90])[CH:85]([NH2:89])[CH2:86][CH2:87][CH3:88])[CH3:81]>O.ClCCl.CN(C)C=O>[CH2:80]([O:82][C:83](=[O:91])[CH:84]([OH:90])[CH:85]([NH:89][C:23]([CH:15]1[CH2:16][CH:17]2[CH:22]([CH2:21][CH2:20][CH2:19][CH2:18]2)[N:14]1[C:12](=[O:13])[CH:11]([NH:10][C:8](=[O:9])[CH:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[NH:30][C:31]([C:33]1[CH:38]=[N:37][CH:36]=[CH:35][N:34]=1)=[O:32])[C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:86][CH2:87][CH3:88])[CH3:81]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2724699PyBOPHCID 684917401-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acidHCID 85806087Ethyl 3-amino-2-hydroxyhexanoate hydrochloride

Product 1

HCID 67114148HCID 67114148, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

In a dry flask charged with a 1:1 mixture of dichloromethane-dimethylformamide (100 ml) was placed 1-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid 32a (2.0 g, 4.28 mmols), PyBOP (2.5 g, 4.7 mmol), and N-methyl-morpholine (2.4 ml, 21.4 mmol) and the reaction placed under an atmosphere of nitrogen. In a 100 mL addition funnel was placed a solution of the amine 14(1.0 g, 4.7 mmols) and N-methyl-morpholine (0.60 ml, 5.35 mmol) in a 1:1 mixture of dichloromethane-dimethylformamide (10 ml). The reaction was cooled to 0° C., and the amine was added while maintaining the temperature at 0° C. The reaction was allowed to warm to ambient temperature as it was stirred over night. HPLC analysis showed the reaction to be complete, and then the reaction was diluted with water to 500 mL. After stirring the precipitate was filtered and dried to give 2.4 g (82% yield) of 32 as a beige solid. This material was used as is in the next step without further purification. HPLC: RT=5.66 min, (10-90% acetonitrile-water over 7 minutes); LC/MS: retention time 3.94 min (10-90% acetonitrile-water over 5 minutes); M+H+=685.5.

Workup

  1. additionIn a 100 mL addition funnel
  2. temperaturewhile maintaining the temperature at 0° C
  3. temperatureto warm to ambient temperature as it
  4. customthe reaction
  5. stirringAfter stirring the precipitate
  6. filtrationwas filtered
  7. customdried

Sources & evidence

ORD record
ord-e6009ce13687449ebf31cfe81f1476e0
Source dataset
uspto-grants-2013_09
Patent number
US08536136B2

Reaction notes

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