Trifluoroacetic acid → N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499586Notes

Reaction equation

HRID 1499586 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][CH3:10])[CH:5]=[C:4]([F:11])[C:3]=1[C:12]1[N:17]=[C:16]([C:18]([NH:20][C:21]2[C:22]([N:31]3[CH2:36][C@H:35]([CH3:37])[CH2:34][C@H:33]([NH:38]C(=O)OC(C)(C)C)[CH2:32]3)=[C:23]3[CH2:29][CH2:28][CH:27]([OH:30])[C:24]3=[N:25][CH:26]=2)=[O:19])[CH:15]=[CH:14][C:13]=1[F:46].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:38][C@H:33]1[CH2:34][C@@H:35]([CH3:37])[CH2:36][N:31]([C:22]2[C:21]([NH:20][C:18]([C:16]3[CH:15]=[CH:14][C:13]([F:46])=[C:12]([C:3]4[C:2]([F:1])=[CH:7][C:6]([CH2:8][O:9][CH3:10])=[CH:5][C:4]=4[F:11])[N:17]=3)=[O:19])=[CH:26][N:25]=[C:24]3[CH:27]([OH:30])[CH2:28][CH2:29][C:23]=23)[CH2:32]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726806tert-butyl ((3S,5R)-1-{3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

Product 1

HCID 86726807N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The alcohol intermediated was treated with TFA (6 mL) and DCM (6 mL). The mixture was stirred at room temperature for 2 h, and then concentrated under reduced pressure. The resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to afford two diastereoisomers of the title compound as white powders.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-5557799fcc9b437798a90048d2c08954
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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