Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-(4-(Benzyloxy)-3,5-dimethylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177567Notes

Reaction equation

HRID 1177567 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13](O)=O)=[CH:11][C:10]=1[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:24][C:25]1[C:26](=[S:40])[NH:27][C:28]([C:31]2([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:33][CH2:32]2)=[CH:29][CH:30]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13]2[S:40][C:26]3[C:25]([N:24]=2)=[CH:30][CH:29]=[C:28]([C:31]2([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH2:32][CH2:33]2)[N:27]=3)=[CH:11][C:10]=1[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24386Thionyl ChlorideHCID 27339934-Benzyloxy-3,5-dimethylbenzoic acidHCID 591748363-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione

Product 1

HCID 671117832-(4-(Benzyloxy)-3,5-dimethylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-(benzyloxy)-3,5-dimethylbenzoic acid (238.0 mg, 929 μmol) and thionyl chloride (2.5 mL, 34.25 mmol) was heated at 70° C. for 1 h and then concentrated in vacuo. 3-Amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione (225 mg, 0.929 mmol) was added to the residue, and the resulting mixture was and heated in toluene (9.0 mL) at 100° C. for 10 min. (±)-10-Camphorsulfonic acid (194 mg, 836 μmol) was subsequently added, and the resulting mixture was heated at 100° C. for 30 min. The reaction solution was then cooled to 25° C. and concentrated onto silica gel. Chromatographic purification (silica gel, 0-40% ethyl ether/hexanes) provided 2-(4-(benzyloxy)-3,5-dimethylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine as a white solid. MS (ESI) m/z: Calculated: 462.2; Observed: 463.2 (M++1).

Workup

  1. concentrationconcentrated in vacuo
  2. additionwas subsequently added
  3. temperaturethe resulting mixture was heated at 100° C. for 30 min
  4. temperatureThe reaction solution was then cooled to 25° C.
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0-40% ethyl ether/hexanes)

Sources & evidence

ORD record
ord-aac157490ff34fc1a3d5fcb41994c11b
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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