1,1'-Carbonyldiimidazole → HCID 86726342, compound

HRID 629742Notes

Reaction equation

HRID 629742 reaction equation
C(OC(N[C@H:9]([C:25]([NH:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([F:51])[C:33]=1[CH2:34][CH2:35][C@H:36]1[O:41][CH2:40][C@@H:39]([CH2:42][OH:43])[N:38](C(OC(C)(C)C)=O)[CH2:37]1)=[O:26])[CH:10]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=O)(C)(C)C.[C:52](N1C=CN=C1)(N1C=CN=C1)=[O:53].[Cl:64][C:65]1[N:70]=[C:69]([CH2:71][NH2:72])[CH:68]=[CH:67][CH:66]=1>N1C=CC=CC=1>[Cl:64][C:65]1[N:70]=[C:69]([CH2:71][NH:72][C:52](=[O:53])[O:43][CH2:42][C@@H:39]2[CH2:40][O:41][C@H:36]([CH2:35][CH2:34][C:33]3[C:32]([F:51])=[CH:31][N:30]=[CH:29][C:28]=3[NH:27][C:25](=[O:26])[CH2:9][CH:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:37][NH:38]2)[CH:68]=[CH:67][CH:66]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 10313191(6-Chloropyridin-2-yl)methanamineHCID 86726337HCID 86726337, compound

Product 1

HCID 86726342HCID 86726342, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of tert-Butyl (2R,5R)-2-[2-(3-{[N-(tert-butoxycarbonyl)-4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]amino}-5-fluoropyridin-4-yl)ethyl]-5-(hydroxymethyl)morpholine-4-carboxylate (Example 149, Step 7) (677 mg, 0.95 mmol) and carbonyldiimidazole (154 mg, 0.95 mmol) was added dry pyridine (22.5 mL). The resulting solution was heated at 60° C. and stirred for 2 h. This solution was then distributed in 0.5 mL (0.021 mmol) aliquots to 45 2-dram sample vials, each containing a diverse amine (0.042 mmol); among them (6-chloropyridin-2-yl)methanamine. The resulting mixtures were stirred at 60° C. for 3 h. Solvent was removed under stream of N2 gas. The residues were diluted with 4 N HCl/diethyl ether (1 mL) and stirred at room temperature for 16 h. Solvent was removed under stream of N2 gas, and the residues were diluted with DMSO and purified by mass-guided reversed-phase HPLC (10-90% CH3CN:0.1% NH4OH/H2O). HRMS (ES) 683.2353 (M+H). found, 683.2355 required.

Workup

  1. stirringThe resulting mixtures were stirred at 60° C. for 3 h
  2. customSolvent was removed under stream of N2 gas
  3. additionThe residues were diluted with 4 N HCl/diethyl ether (1 mL)
  4. stirringstirred at room temperature for 16 h
  5. customSolvent was removed under stream of N2 gas
  6. additionthe residues were diluted with DMSO
  7. custompurified by mass-guided reversed-phase HPLC (10-90% CH3CN:0.1% NH4OH/H2O)

Sources & evidence

ORD record
ord-2446a8c255c64da9916cf6108b50807f
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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