Ammonia → HCID 68277870, compound

HRID 1467915Notes

Reaction equation

HRID 1467915 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, compoundHCID 86691618HCID 86691618, compound

Product 1

HCID 68277870HCID 68277870, compoundYield 34.8%

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-9600647e887f42afad7441eeaa4e3a17
Source dataset
uspto-grants-2015_04
Patent number
US09000181B2

Reaction notes

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