Triethylamine → HCID 86621264, compound

HRID 1672925Notes

Reaction equation

HRID 1672925 reaction equation
[F:1][C:2]1[C:3]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH:16]([OH:18])[CH3:17])([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH:28]([C:31]1[CH:36]=[C:35]([CH:37]([CH3:39])[CH3:38])[CH:34]=[C:33]([CH:40]([CH3:42])[CH3:41])[C:32]=1[S:43](Cl)(=[O:45])=[O:44])([CH3:30])[CH3:29].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:30][CH:28]([C:31]1[CH:36]=[C:35]([CH:37]([CH3:38])[CH3:39])[CH:34]=[C:33]([CH:40]([CH3:42])[CH3:41])[C:32]=1[S:43]([O:18][CH:16]([C:13]1([OH:15])[CH2:14][N:11]([C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[C:3]=2[NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])=[O:10])[CH2:12]1)[CH3:17])(=[O:44])=[O:45])[CH3:29]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chloride3×HCID 67051573HCID 67051573, compound

Product 1

HCID 86621264HCID 86621264, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-hydroxyethyl)azetidin-3-ol (267 mg, 0.543 mmol), was dissolved in dichloromethane (10 mL) and treated with 4-(dimethylamino)pyridine (80 mg, 0.661 mmol) and 2,4,6-triisopropylbenzenesulfonyl chloride (183 mg, 0.604 mmol) at ambient for 15 h. Triethylamine (0.076 mL, 0.545 mmol) was added and the mixture was stirred at ambient for 3 h and then at 35° C. for 4 h and then at ambient for a further 15 h. 2,4,6-Triisopropylbenzenesulfonyl chloride (110 mg, 0.363 mmol) was added and the mixture was stirred at 35° C. for 3 h and then 4-(dimethylamino)pyridine (80 mg, 0.661 mmol) was added and the mixture was stirred at 35° C. for 2 h. 2,4,6-Triisopropylbenzenesulfonyl chloride (303 mg, 1.0 mmol) was added and the mixture was stirred at 35° C. for a further 18 h. The mixture was adsorbed on to silica and purified by column chromatography (silica gel, 30-50% ethyl acetate in hexanes) to give 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl 2,4,6-tris(1-methylethyl)benzenesulfonate (201 mg, 0.265 mmol, 49% yield): MS (EI) for C33H38F3IN2O5S: 759 (MH+).

Workup

  1. waitat 35° C. for 4 h
  2. waitat ambient for a further 15 h
  3. stirringthe mixture was stirred at 35° C. for 3 h
  4. stirringthe mixture was stirred at 35° C. for 2 h
  5. stirringthe mixture was stirred at 35° C. for a further 18 h
  6. custompurified by column chromatography (silica gel, 30-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9940bb3e4c4b4d1187372a63c5d21d5d
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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