Sodium cyanoborohydride → (2s,4r)-4-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-methylpyrrolidine-2-carboxylic acid trifluoroacetic acid salt

HRID 1177537Notes

Reaction equation

HRID 1177537 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([C@@H:33]2[CH2:37][NH:36][C@H:35]([C:38]([OH:40])=[O:39])[CH2:34]2)[CH:12]=[CH:13][C:14]=1[C:15]1[S:16][C:17]2[C:22]([N:23]=1)=[CH:21][CH:20]=[C:19]([C:24]1([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:26][CH2:25]1)[N:18]=2.[C:41]([BH3-])#N.[Na+]>C(#N)C>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([C@@H:33]2[CH2:37][N:36]([CH3:41])[C@H:35]([C:38]([OH:40])=[O:39])[CH2:34]2)[CH:12]=[CH:13][C:14]=1[C:15]1[S:16][C:17]2[C:22]([N:23]=1)=[CH:21][CH:20]=[C:19]([C:24]1([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][CH2:26]1)[N:18]=2

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 67111535(2s,4r)-4-(3-Fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)pyrrolidine-2-carboxylic acid trifluoroacetic acid salt

Product 1

HCID 67111611(2s,4r)-4-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-methylpyrrolidine-2-carboxylic acid trifluoroacetic acid salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a slurry of (2S,4R)-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)pyrrolidine-2-carboxylic acid trifluoroacetic acid salt (0.048 g, 0.084 mmol) formaldehyde (0.050 mL, 0.67 mmol) acetic acid (0.048 mL, 0.84 mmol) in 2 mL ACN was added sodium cyanoborohydride (0.011 g, 0.17 mmol). After 1 h, the reaction mixture was concentrated, dissolved in DMSO/TFA, and purified by RPHPLC, gradient of ACN/TFA in H2O/TFA to give (2S,4R)-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-methylpyrrolidine-2-carboxylic acid trifluoroacetic acid salt as a solid. MS (ESI) m/z: Calculated: 473.2; Observed: 474.1 (M++1).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutiondissolved in DMSO/TFA
  3. custompurified by RPHPLC, gradient of ACN/TFA in H2O/TFA

Sources & evidence

ORD record
ord-277132ccc4a843319c49e0fe0bfbf36b
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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