Methyl pyrrolidine-3-carboxylate hydrochloride → HCID 67111608, compound

HRID 1177421Notes

Reaction equation

HRID 1177421 reaction equation
FC1C=C(C=CC=1C1SC2C(N=1)=CC=C(C1(C3C=CC=CC=3)CC1)N=2)C=O.Cl.COC(C1CCNC1)=O.[F:38][C:39]1[CH:40]=[C:41]([CH2:63][N:64]2[CH2:68][CH2:67][CH:66]([C:69]([O:71][CH3:72])=[O:70])[CH2:65]2)[CH:42]=[CH:43][C:44]=1[C:45]1[S:46][C:47]2[C:52]([N:53]=1)=[CH:51][CH:50]=[C:49]([C:54]1([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH2:56][CH2:55]1)[N:48]=2>>[F:38][C:39]1[CH:40]=[C:41]([CH2:63][N:64]2[CH2:68][CH2:67][C@@H:66]([C:69]([O:71][CH3:72])=[O:70])[CH2:65]2)[CH:42]=[CH:43][C:44]=1[C:45]1[S:46][C:47]2[C:52]([N:53]=1)=[CH:51][CH:50]=[C:49]([C:54]1([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH2:55][CH2:56]1)[N:48]=2.[F:38][C:39]1[CH:40]=[C:41]([CH2:63][N:64]2[CH2:68][CH2:67][C@H:66]([C:69]([O:71][CH3:72])=[O:70])[CH2:65]2)[CH:42]=[CH:43][C:44]=1[C:45]1[S:46][C:47]2[C:52]([N:53]=1)=[CH:51][CH:50]=[C:49]([C:54]1([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH2:55][CH2:56]1)[N:48]=2

Participants

5

Reactant 3

HCID 19261352Methyl pyrrolidine-3-carboxylate hydrochlorideHCID 591749073-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehydeHCID 67111607HCID 67111607, compound

Product 2

HCID 67111608HCID 67111608, compoundHCID 67112630HCID 67112630, compound

Procedure

Reaction of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)-benzaldehyde (0.300 g, 0.801 mmol) and methylpyrrolidine-3-carboxylate hydrochloride (0.199 g, 1.20 mmol), according to Reference R and general procedure for reductive amination afforded the racemic mixture of methyl 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)pyrrolidine-3-carboxylate. MS (ESI) m/z: Calculated: 487.2; Observed: 488.0 (M++1). The enantiomers of methyl 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)pyrrolidine-3-carboxylate were separated by SFC chromatography (Column: Chiralpak AS-H (21×250 mm, 5 um); A: Liquid CO2; B: Isopropanol (0.2% DEA); Isocratic: 56:44 (A:B); Flow rate: 70 mL/min; Outlet Pressure: 100 bar) to give (R)-methyl 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)pyrrolidine-3-carboxylate and (S)-methyl 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)pyrrolidine-3-carboxylate.

Workup

  1. customamination afforded
  2. customThe enantiomers of methyl 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)pyrrolidine-3-carboxylate were separated by SFC chromatography (Column

Sources & evidence

ORD record
ord-63d95bc4560a44aca97af2e4664f2a20
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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