Pyridine → HCID 86627964, compound

HRID 251741Notes

Reaction equation

HRID 251741 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:13][C:14]([NH:16][C@H:17]([C:26]1[NH:27][C:28]([C:31]2[CH:40]=[CH:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:32]=2)=[CH:29][N:30]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24])=[O:15].[F:41][C:42]([F:47])([F:46])[C:43]([O-:45])=[O:44].C(CCCCC[C@@H](C1[NH2+]C(C2C=CC3C(=CC=CC=3)C=2)=CN=1)NC(=O)CC1C2C(=CC=C(OC)C=2)NC=1C)(O)=O.C([O-])([O-])=O.[Na+].[Na+].C(OC(C(F)(F)F)=O)([C:96]([F:99])([F:98])[F:97])=O.N1C=CC=CC=1>CCO.O>[F:41][C:42]([F:47])([F:46])[C:43]([O-:45])=[O:44].[CH:40]1[C:39]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:33]=[CH:32][C:31]=1[C:28]1[NH2+:27][C:26]([C@@H:17]([NH:16][C:14](=[O:15])[CH2:13][C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=3)[NH:8][C:7]=2[CH3:12])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](=[O:24])[C:96]([F:99])([F:98])[F:97])=[N:30][CH:29]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 10340Sodium CarbonateHCID 44574065HCID 44574065, compoundHCID 87331357HCID 87331357, compound

Product 1

HCID 86627964HCID 86627964, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of (7S)-7-{[(5-methoxy-2-methyl-1H-indol-3-yl)acetyl]amino}-7-[5-(2-naphthyl)-1H-imidazol-2-yl]heptanoic acid (Free base of Example 107) (1 eq.) in EtOH (0.5 M solution) was added Na2CO3 (1 eq.). The heterogeneous mixture was stirred 40 min at RT then the solvent was removed under reduced pressure. DCM was added (0.14 M solution), the mixture was cooled at 0° C. with an ice-bath then TFAA (6 eq.) was added followed by pyridine (8 eq.). After 40 min at the same temperature some water was added and the product extracted with DCM. The collected organic phase were treated with brine and dried (Na2SO4) and after removing the solvent under reduced pressure the crude was purified by preparative RP-HPLC, using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents (column: C18). The desired fractions were lyophilized to afford the titled compound as a white powder as a mixture of the ketone and hydrated form 1H NMR (500 MHz, pyridine) δ: 11.65-11.55 (0.5H, m), 11.50-11.38 (0.5H, m), 9.21-9.12 (0.5H, m), 8.71-8.63 (2H, m), 8.30-8.10 (1.5H, m), 8.00-7.79 (4.5H, m), 7.56-7.30 (4H, m), 7.09-6.97 (1H, m), 5.76-5.62 (1H, m), 4.11-3.96 (1.5, m), 3.85-3.71 (2.5H, m) 2.71-2.58 (1H, m), 2.55-2.41 (3.5H, m), 2.40-2.23 (2H, m), 2.21-2.03 (2H, m), 2.10-1.79 (1.5H, m), 1.70-1.00 (6H, m). MS (ES) C33H33F3N4O3 requires: 590, found: 609 (M+H2O+H)+.

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionDCM was added (0.14 M solution)
  3. temperaturethe mixture was cooled at 0° C. with an ice-bath
  4. extractionthe product extracted with DCM
  5. additionThe collected organic phase were treated with brine
  6. dry with materialdried (Na2SO4)
  7. customafter removing the solvent under reduced pressure the crude
  8. customwas purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-8c6f62e8b29a42f297899748768eecdf
Source dataset
uspto-grants-2011_01
Patent number
US07863294B2

Reaction notes

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