Methanesulfonyl chloride → HCID 73053993, compound

HRID 1846216Notes

Reaction equation

HRID 1846216 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C@@:11]2([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[C:23]([F:32])[CH:22]=3)[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[O:14][CH2:13][CH2:12]2)=[O:9])=[N:6][CH:7]=1.[CH3:33][S:34](Cl)(=[O:36])=[O:35].CCN(C(C)C)C(C)C>C(Cl)Cl.[OH-].[Na+]>[F:32][C:23]1[CH:22]=[C:21]([C@:11]2([NH:10][C:8](=[O:9])[C:5]3[CH:4]=[CH:3][C:2]([NH:1][S:34]([CH3:33])(=[O:36])=[O:35])=[CH:7][N:6]=3)[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[O:14][CH2:13][CH2:12]2)[CH:26]=[CH:25][C:24]=1[O:27][C:28]([F:31])([F:30])[F:29]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 89964666HCID 89964666, compound

Product 1

HCID 73053993HCID 73053993, compound

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-5-amino-N-(4-(3-fluoro-4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)picolinamide (44 mg, 0.098 mmol) in DCM (0.6 mL) were added methanesulfonyl chloride (8.40 μl, 0.128 mmol) and DIEA (0.022 mL, 0.128 mmol). The resulting mixture was stirred at room temperature overnight. A solution of NaOH (10 N, 2 drops) was added, and the resulting mixture was stirred at room temperature for 2 h. The reaction mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by prep HPLC (0-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 527.0 (MH+). 1H NMR (400MHz, d4-MeOH) δ: 8.48 (d, J=2.3 Hz, 1H), 8.30 (dd, J=4.5, 1.4 Hz, 1H), 8.05 (d, J=8.6 Hz, 1H), 7.83 (dd, J=8.6, 2.5 Hz, 1H), 7.37-7.62 (m, 4H), 7.25 (d, J=8.6 Hz, 1H), 4.47 (dt, J=11.9, 4.4 Hz, 1H), 4.05-4.26 (m, 1H), 3.12-3.25 (m, 2H), 3.10 (s, 3H).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 2 h
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customThe residue was purified by prep HPLC (0-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-17c6225bd2e64e0486572971e19caf0c
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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