Acetic Acid → Methyl 1-((4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate

HRID 1177408Notes

Reaction equation

HRID 1177408 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][C:12]=3[F:19])=[N:10][C:5]2=[CH:4][CH:3]=1.Cl.[NH:21]1[CH2:24][CH:23]([C:25]([O:27][CH3:28])=[O:26])[CH2:22]1.C(N(C(C)C)C(C)C)C.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCl.CO>[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH2:15][N:21]4[CH2:24][CH:23]([C:25]([O:27][CH3:28])=[O:26])[CH2:22]4)=[CH:13][C:12]=3[F:19])=[N:10][C:5]2=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 21100040Methyl azetidine-3-carboxylate hydrochlorideHCID 866387064-(5-Chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorobenzaldehyde

Product 1

HCID 86638707Methyl 1-((4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorobenzaldehyde (2.08 g, 7.11 mmol), methyl azetidine-3-carboxylate hydrochloride (1.62 g, 10.7 mmol), N-ethyl-N-isopropylpropan-2-amine (1.86 mL, 10.7 mmol) in dichloromethane (40.00 mL) and methanol (30.00 mL) was stirred for 5 min. Then acetic acid (1.64 mL, 28.4 mmol) was added and the mixture was allowed to stir for 90 min at 50° C. Sodium cyanoborohydride (0.223 g, 3.55 mmol) was added. After 15 min, the solvent removed, and the mixture concentrated onto silica gel. Purification by silica gel chromatography, 120 g column, 30-40% EtOAc/hex followed by 50-60% (3% TEA in EtOAc/hex) gave methyl 1-((4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate. MS (ESI) m/z: calculated: 391.1; Observed: 392.0 (M++1).

Workup

  1. stirringto stir for 90 min at 50° C
  2. waitAfter 15 min
  3. customthe solvent removed
  4. concentrationthe mixture concentrated onto silica gel
  5. customPurification by silica gel chromatography, 120 g column, 30-40% EtOAc/hex

Sources & evidence

ORD record
ord-5b21c1c25c3c4b72b0cd46b965e1cf2f
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…