Water → HCID 178419950, compound

HRID 1846783Notes

Reaction equation

HRID 1846783 reaction equation
[H-].[Na+].[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[NH:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]1.[O:20]1[CH2:25][CH:24]=[C:23]([C:26]2[C:27](F)=[N:28][CH:29]=[CH:30][CH:31]=2)[CH2:22][CH2:21]1.O>CN1C(=O)CCC1>[O:20]1[CH:21]=[CH:22][CH:23]([C:26]2[C:27]([O:19][C@H:16]3[CH2:15][CH2:14][C@H:13]([NH:12][C:4]4[S:3][C:7]5[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=5[N:5]=4)[CH2:18][CH2:17]3)=[N:28][CH:29]=[CH:30][CH:31]=2)[CH2:24][CH2:25]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 593267823-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridineHCID 178521592HCID 178521592, compound

Product 1

HCID 178419950HCID 178419950, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Sodium hydride (0.054 g, 1.3 mmol, 60% dispersion in mineral oil) was added to a mixture of trans-4-(benzo[d]thiazol-2-ylamino)cyclohexanol (0.17 g, 0.67 mmol) in NMP (1.5 mL) in a microwave tube. The tube was sealed and placed under an argon atmosphere. The mixture was stirred at RT for 45 min before 3-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridine, as prepared in preparation 1a, step 1, (0.10 g, 0.56 mmol) was added via syringe. The reaction mixture was warmed to 120° C. and stirred for 1 h. Water was added, and the aqueous mixture was extracted with EtOAc (2×). The organic extracts were combined, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified via silica gel chromatography to give both N-(trans-4-(3-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclohexyl)benzo[c/]thiazol-2-amine and N-(trans-4-(3-(3,4-dihydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclohexyl)benzo[d]thiazol-2-amine as white solids. [M+1] 408.1 each. IC50 (uM): 0.007281 (Example 3b) and 0.9154 (Example 3c).

Workup

  1. customThe tube was sealed
  2. additionwas added via syringe
  3. extractionthe aqueous mixture was extracted with EtOAc (2×)
  4. washwashed with saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product was purified via silica gel chromatography

Sources & evidence

ORD record
ord-744832b2aa2f4927a885b6b1b9fe4956
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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