p-Toluenesulfonic acid → HCID 46912889, compound

HRID 1626585Notes

Reaction equation

[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].CCN(CC)CC.[F:36][C:37]([F:48])([F:47])[CH2:38]OS(C(Cl)(Cl)Cl)(=O)=O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CO.CS(C)=O>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][N:20]([CH2:38][C:37]([F:48])([F:47])[F:36])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (example 7) (200 mg, 0.48 mmol) and Et3N (133 μL, 0.95 mmol). in toluene (1.5 mL) was added 2,2,2-trifluoroethyltrichloromethane sulfonate (91 μL, 0.95 mmol) and DMSO (0.5 mL). The reaction mixture was heated to 100° C. overnight. The reaction was cooled, diluted with methanol and adsorbed onto a mp-TsOH cartridge (2.5 g, 3 mmol/g). The cartridge was rinsed with MeOH (3 column volumes) and the product was eluted with 7M NH3 in MeOH. The basic fractions were concentrated in vacuo and purified by prep HPLC (low pH) to give the desired product (2.1 mg, 0.9% yield).

Workup

temperatureThe reaction was cooled
washThe cartridge was rinsed with MeOH (3 column volumes)
washthe product was eluted with 7M NH3 in MeOH
concentrationThe basic fractions were concentrated in vacuo
custompurified by prep HPLC (low pH)

Sources & evidence

ORD record: ord-e9a57d0b3c8a45009e9c572dbfd9344a
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785457B2

Reaction notes

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