Methanesulfonyl chloride → tert-Butyl 4-(1-(3-((methylsulfonyloxy)methyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

HRID 1971397Notes

Reaction equation

HRID 1971397 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[C:27]5[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][C:28]=5[N:29]=[CH:30][N:31]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.[CH3:52][S:53](Cl)(=[O:55])=[O:54]>C(Cl)Cl.CCOC(C)=O>[CH3:52][S:53]([O:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[C:27]5[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][C:28]=5[N:29]=[CH:30][N:31]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1)(=[O:55])=[O:54]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59394261HCID 59394261, compound

Product 1

HCID 59394300tert-Butyl 4-(1-(3-((methylsulfonyloxy)methyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 4-(1-(3-(hydroxymethyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (0.211 g, 0.361 mmol) in 6 mL of DCM with DIEA (0.19 mL, 1.08 mmol) at 0° C., methanesulfonyl chloride (0.037 mL, 0.469 mmol) is added and the reaction stirred for 3 h. At that point the reaction is diluted with EtOAc, washed with saturated sodium bicarbonate, brine and the organic layer is dried over sodium sulfate. Concentration provides a mixture of the title compound and tert-butyl 4-(1-(3-(chloromethyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-a]pyrimidine-7(8H)-carboxylate (3:7), which is carried on to next step.

Workup

  1. washwashed with saturated sodium bicarbonate, brine
  2. dry with materialthe organic layer is dried over sodium sulfate
  3. concentrationConcentration
  4. customprovides

Sources & evidence

ORD record
ord-a3484a9a61cf4849a054711ce6519b1f
Source dataset
uspto-grants-2013_04
Patent number
US08431584B2

Reaction notes

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