1,1'-Thiocarbonyldi-2(1H)-pyridone → 2-(4-(4-(2-(5-Cyclobutyl-1,3,4-thiadiazol-2-ylamino)pyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetic acid

HRID 881722Notes

Reaction equation

HRID 881722 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]34[CH2:21][CH2:20][C:17]([CH2:22][C:23]([O:25]C)=[O:24])([CH2:18][CH2:19]3)[O:16][CH2:15]4)=[CH:10][CH:9]=2)=[CH:4][N:3]=1.[C:27](N1C=CC=CC1=O)(N1C=CC=CC1=O)=[S:28].[CH:43]1([C:47]([NH:49][NH2:50])=O)[CH2:46][CH2:45][CH2:44]1>ClCCl>[CH:43]1([C:47]2[S:28][C:27]([NH:1][C:2]3[N:7]=[CH:6][C:5]([C:8]4[CH:9]=[CH:10][C:11]([C:14]56[CH2:21][CH2:20][C:17]([CH2:22][C:23]([OH:25])=[O:24])([CH2:18][CH2:19]5)[O:16][CH2:15]6)=[CH:12][CH:13]=4)=[CH:4][N:3]=3)=[N:50][N:49]=2)[CH2:46][CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 8531621,1'-Thiocarbonyldi-2(1H)-pyridoneHCID 969366CyclobutanecarbohydrazideHCID 86700829Methyl 2-(4-(4-(2-aminopyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

Product 1

HCID 721883882-(4-(4-(2-(5-Cyclobutyl-1,3,4-thiadiazol-2-ylamino)pyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetic acidYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a reaction vial containing methyl 2-(4-(4-(2-aminopyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (40 mg, 0.11 mmol) was added dichloromethane (1 ml) at room temperature. 1,1′-thiocarbonyldipyridin-2(1H)-one (29 mg, 0.12 mmol) was added and the resulting mixture was heated to 50° C. for overnight. The mixture was cool down to room temperature and cyclobutanecarbohydrazide (19 mg, 0.17 mmol) was then added and stirred at room temperature for another hour. The content was then concentrated to dryness and the resulting residue was taken up in MeOH to form a nice slurry. The slurry was filtered and washed with small amount of MeOH to afford the title compound as off-white solid after drying (48 mg, 83% yield). LC/MS, ESI-MS(+): 510.4, RT: 1.26 (Condition E)

Workup

  1. temperatureThe mixture was cool down to room temperature
  2. concentrationThe content was then concentrated to dryness
  3. customto form a nice slurry
  4. filtrationThe slurry was filtered
  5. washwashed with small amount of MeOH

Sources & evidence

ORD record
ord-45297966a341431fa1d42fbd9adc6ee5
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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