Water → Methyl 1-((3-fluoro-4-(5-(1-(4-hydroxyphenyl)cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)-azetidine-3-carboxylate

HRID 1177497Notes

Reaction equation

HRID 1177497 reaction equation
O.C([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:19]3[N:24]=[C:23]4[S:25][C:26]([C:28]5[CH:42]=[CH:41][C:31]([CH2:32][N:33]6[CH2:36][CH:35]([C:37]([O:39][CH3:40])=[O:38])[CH2:34]6)=[CH:30][C:29]=5[F:43])=[N:27][C:22]4=[CH:21][CH:20]=3)[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)C1C=CC=CC=1.C(N(CC)CC)C>C1COCC1.CO.C(Cl)Cl.[Pd]>[F:43][C:29]1[CH:30]=[C:31]([CH2:32][N:33]2[CH2:34][CH:35]([C:37]([O:39][CH3:40])=[O:38])[CH2:36]2)[CH:41]=[CH:42][C:28]=1[C:26]1[S:25][C:23]2[C:22]([N:27]=1)=[CH:21][CH:20]=[C:19]([C:16]1([C:13]3[CH:12]=[CH:11][C:10]([OH:9])=[CH:15][CH:14]=3)[CH2:18][CH2:17]1)[N:24]=2

Participants

7

Reactant 3

HCID 962WaterHCID 8471TriethylamineHCID 67111767Methyl 1-(4-(5-(1-(4-(benzyloxy)phenyl)cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate

Product 1

HCID 67111906Methyl 1-((3-fluoro-4-(5-(1-(4-hydroxyphenyl)cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)-azetidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A slurry of palladium 10% on carbon, 50% water (0.26 g), methyl 1-(4-(5-(1-(4-(benzyloxy)phenyl)cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate (0.144 g, 0.25 mmol), triethylamine (0.087 mL, 0.62 mmol) in 4 mL of 3:1 THF/MeOH was stirred rapidly under an atmosphere of hydrogen (balloon) for 36 h. The reaction mixture was diluted with DCM, and filtered through celite and concentrated in vacuo. The resulting solid was adsorbed onto 1.4 g silica gel and purified by silica gel chromatography 0-100% EA/hexanes, to give methyl 1-((3-fluoro-4-(5-(1-(4-hydroxyphenyl)cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)-azetidine-3-carboxylate as a white solid. MS (ESI) m/z: calculated: 489.2; Observed: 490.1 (M++1).

Workup

  1. filtrationfiltered through celite and
  2. concentrationconcentrated in vacuo
  3. custompurified by silica gel chromatography 0-100% EA/hexanes

Sources & evidence

ORD record
ord-8ed90314e7bc4f3db3c3c2cc0c7b95ef
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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