Water → HCID 178480290, compound

HRID 536728Notes

Reaction equation

HRID 536728 reaction equation
[NH:1]1[CH2:4][CH2:3][C@H:2]1[CH2:5][O:6][C:7]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:8]=1[C:9](/[N:11]=[C:12]1/[N:13]([CH2:22][CH:23]2[CH2:25][CH2:24]2)[N:14]([CH3:21])[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:16]/1)=[O:10].C(N(CC)CC)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43].O>C(Cl)Cl>[C:17]([C:15]1[N:14]([CH3:21])[N:13]([CH2:22][CH:23]2[CH2:24][CH2:25]2)/[C:12](=[N:11]/[C:9](=[O:10])[C:8]2[CH:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:29][C:7]=2[O:6][CH2:5][C@@H:2]2[CH2:3][CH2:4][N:1]2[S:42]([CH3:41])(=[O:44])=[O:43])/[CH:16]=1)([CH3:19])([CH3:18])[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 178480289HCID 178480289, compound

Product 1

HCID 178480290HCID 178480290, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Example 63B (220 mg, 0.474 mmol) and triethylamine (0.132 ml, 0.947 mmol) in CH2Cl2 (6 ml) was added methanesulfonyl chloride (0.055 ml, 0.710 mmol) dropwise. The mixture was stirred at ambient temperature for 2 hours then portioned between CH2Cl2 and water. The organic extract was washed with brine and concentrated. Purification by chromatography (silica gel, MeOH/Et3N (9:1) in CH2Cl2 in 0-30% gradient) provided 160 mg (62% yield) of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.41-0.68 (m, 4H), 1.01-1.18 (m, 1H), 1.41-1.49 (m, 9H), 2.25-2.45 (m, 2H), 2.91 (s, 3H), 3.71-3.80 (m, 1H), 3.83 (s, 3H), 3.93-4.07 (m, 1H), 4.14-4.33 (m, 4H), 4.59-4.80 (m, 1H), 6.95-7.06 (m, 2H), 7.50 (dd, J=8.82, 1.70 Hz, 1H), 7.92 (d, J=2.37 Hz, 1H); MS (DCI/NH3) m/z 543 (M+H)+.

Workup

  1. extractionThe organic extract
  2. washwas washed with brine
  3. concentrationconcentrated
  4. customPurification by chromatography (silica gel, MeOH/Et3N (9:1) in CH2Cl2 in 0-30% gradient)

Sources & evidence

ORD record
ord-77bc9806dec842479960e84148b5900d
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

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