Chlorosuccinimide → HCID 71267858, compound

HRID 1630315Notes

Reaction equation

HRID 1630315 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:45])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](=[O:44])[NH:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[C:38]([CH3:43])[CH:37]=3)[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Cl:53])C(=O)C1>C(O)(=O)C.C(Cl)Cl>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:45])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](=[O:44])[NH:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[C:38]([CH3:43])[CH:37]=3)[C:32]=2[Cl:53])[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 86691590HCID 86691590, compound

Product 1

HCID 71267858HCID 71267858, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S)-ethyl 2-(tert-butoxy)-2-(2-((4-fluoro-3-methylbenzyl)carbamoyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (40 mg, 0.064 mmol, 1 equiv) in acetic acid (0.64 mL) was added NCS (10 mg, 0.077 mmol, 1.2 equiv). After stirring 18 h, reaction is pale yellow solution. LCMS indicated complete conversion. The reaction was diluted with DCM and washed with saturated aqueous bicarbonate. The DCM layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (0-10% EtOAc in hexane) to provide desired product as a viscous yellow oil (22 mg, 52% yield). 1H NMR (500 MHz, CDCl3) δ 7.16 (s, 1H), 7.12 (d, J=5.7 Hz, 2H), 6.97 (d, J=9.1 Hz, 1H), 6.83 (d, J=10.6 Hz, 1H), 4.97 (s, 1H), 4.62-4.50 (m, 2H), 4.35 (t, J=5.3 Hz, 2H), 4.19-4.11 (m, 2H), 2.84 (s, 3H), 2.75 (s, 2H), 2.27 (d, J=1.7 Hz, 3H), 2.23-2.13 (m, 2H), 1.80 (s, 3H), 1.29 (t, J=7.1 Hz, 3H), 1.17 (s, 9H); 19F NMR (471 MHz, CDCl3) δ −119.48 (s, 1F), −139.47 (s, 1F); LCMS (ESI, M+1): 655.5.

Workup

  1. customreaction
  2. washwashed with saturated aqueous bicarbonate
  3. dry with materialThe DCM layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash silica gel chromatography (0-10% EtOAc in hexane)

Sources & evidence

ORD record
ord-be3eb47fed4f451aa0c2060237afdc81
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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