Chlorosulfonic acid → HCID 178527433, compound

HRID 403527Notes

Reaction equation

HRID 403527 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]([C:10]2[CH:14]=[CH:13][O:12][N:11]=2)=[CH:8][C:7]([C:15]2[N:20]=[C:19]([OH:21])[CH:18]=[CH:17][N:16]=2)=[N:6]1.[S:26]([Cl:30])(=O)(=[O:28])[OH:27]>C(OCC)(=O)C>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]([C:10]2[CH:14]=[CH:13][O:12][N:11]=2)=[CH:8][C:7]([C:15]2[N:20]=[C:19]([OH:21])[C:18]([S:26]([Cl:30])(=[O:28])=[O:27])=[CH:17][N:16]=2)=[N:6]1

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 178516480HCID 178516480, compound

Product 1

HCID 178527433HCID 178527433, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-ol Compound I-160 (56 mg, 1 equiv) and sulfurochloridic acid (552 μl) in a sealed vial was heated to 100° C. for 30 min. The mixture was diluted in ethyl acetate (50 ml) and washed with water (50 ml). The organic layer was dried, filtered and evaporated to give 79 mg of crude 2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)-4-hydroxypyrimidine-5-sulfonyl chloride as a white solid. The solid was combined with morpholine (47.4 μl, 3.3 equiv) and stirred at 25° C. for 30 min. The mixture was diluted in ethyl acetate (100 ml) and washed with water (50 ml). The organic layer was dried, filtered and evaporated to give crude oil. Purification by column chromatography (0 to 10% methanol in dichloromethane) gave 40 mg of the desired product (45%) as a white solid. 1H NMR (400 MHz, DMSO-d6) 9.11 (d, 1H), 8.01 (bs, 1H), 7.74-7.67 (m, 1H), 7.66 (s, 1H), 7.51 (t, 1H), 7.35-7.30 (m, 1H) 7.22 (s, 1H), 6.33 (bs, 1H), 5.97 (s, 2H), 3.52-3.46 (m, 4H), 2.67-2.59 (m, 4H).

Workup

  1. washwashed with water (50 ml)
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. customevaporated

Sources & evidence

ORD record
ord-8304d6606674461a93ff949cf564ac0b
Source dataset
uspto-grants-2014_06
Patent number
US08748442B2

Reaction notes

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