Ammonia → HCID 68277870, compound

HRID 522626Notes

Reaction equation

HRID 522626 reaction equation
[OH:1][C:2]([C:8]1[S:9][CH:10]=[C:11]([CH3:13])[N:12]=1)([CH3:7])[C:3]([NH:5][NH2:6])=O.[F:14][C:15]1[C:16]([CH2:22][N:23]2[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[S:30])=[N:24]2)=[N:17][CH:18]=[C:19]([F:21])[CH:20]=1.S(=O)(=O)(O)O.N>ClCCl>[F:14][C:15]1[C:16]([CH2:22][N:23]2[CH:27]=[CH:26][C:25]([NH:28][C:29]3[S:30][C:3]([C:2]([C:8]4[S:9][CH:10]=[C:11]([CH3:13])[N:12]=4)([OH:1])[CH3:7])=[N:5][N:6]=3)=[N:24]2)=[N:17][CH:18]=[C:19]([F:21])[CH:20]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 66752196HCID 66752196, compound2×HCID 86691618HCID 86691618, compound

Product 1

HCID 68277870HCID 68277870, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of Intermediate 107, 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanohydrazide (63 mg, 0.313 mmol), and Intermediate 96, 3,5-difluoro-2-[(3-isothiocyanato-1H-pyrazol-1-yl)methyl]pyridine (79 mg, 0.313 mmol) in dichloromethane (anh) (3 mL) was stirred at room temperature overnight. Reaction mixture was concentrated, residue was treated with sulfuric acid (2 mL, 0.364 mmol) and stirred at room temperature during 1 h. Resulting mixture was neutralized with 32% NH3 (aq) under ice-bath until pH was basic. Mixture was partitioned between DCM (3×15 mL) and water (15 mL). Organic phase was separated, dried over magnesium sulfate and concentrated. Residue was purified by preparative HPLC using SUNFIRE column (C18, 3.5 μm, 19×150 mm) and linear gradient 25% to 75% water (0.1% HCOOH)—(0.1% HCOOH). Appropriate fractions were collected to give 1-[5-({1-[(3,5-difluoro-2-pyridinyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol (50 mg, 0.109 mmol, 30.0% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 10.83 (s, 1H), 8.46 (d, 1H), 7.93-7.98 (m, 1H), 7.74 (d, 1H), 7.27 (s, 1H), 7.21 (m, 1H), 5.96 (d, 1H), 5.37 (d, 2H), 2.29 (d, 3H), 1.97 (s, 1H). [ES+MS] m/z 436 (MH+).

Workup

  1. customReaction mixture
  2. concentrationwas concentrated
  3. stirringstirred at room temperature during 1 h
  4. customResulting mixture
  5. customMixture was partitioned between DCM (3×15 mL) and water (15 mL)
  6. customOrganic phase was separated
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customResidue was purified by preparative HPLC
  10. customAppropriate fractions were collected

Sources & evidence

ORD record
ord-8cb1fd20bf6c4b4bb9bd2a90e6997d83
Source dataset
uspto-grants-2016_05
Patent number
US09334265B2

Reaction notes

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