1,2-Dichloroethane → (S)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylurea

HRID 1626550Notes

Reaction equation

HRID 1626550 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[N:15]=[C:16]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]4[CH3:29])[C:17]4[CH2:22][NH:21][CH2:20][C:18]=4[N:19]=3)=[CH:10][CH:9]=2)=[O:6])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[CH:39]1([C:42](O)=[O:43])[CH2:41][CH2:40]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CS(C)=O.O.C(OCC)(=O)C>[CH:39]1([C:42]([N:21]2[CH2:22][C:17]3[C:16]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]4[CH3:29])=[N:15][C:14]([C:11]4[CH:10]=[CH:9][C:8]([NH:7][C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)=[O:6])=[CH:13][CH:12]=4)=[N:19][C:18]=3[CH2:20]2)=[O:43])[CH2:41][CH2:40]1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 15655Cyclopropanecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46894114(S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea

Product 1

HCID 46912282(S)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylureaYield 37%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (example 3) (150 mg, 0.38 mmol) in 2-methyl THF (2 mL) and DMSO (1 mL) was added DIPEA (159 uL, 0.92 mmol), cyclopropane carboxylic acid (578 uL, 0.73 mmol) and EDC (139 mg, 0.73 mmol), followed by HOBt (98 mg, 0.73 mmol). The reaction mixture was stirred at room temperature for 4 h then diluted with water and ethyl acetate. The organic layer was concentrated and purified by prep HPLC (low pH) to give a pale yellow solid (65 mg, 0.14 mmol, 37% yield).

Workup

  1. concentrationThe organic layer was concentrated
  2. custompurified by prep HPLC (low pH)

Sources & evidence

ORD record
ord-fe4e7332113a4d8db0b0e7262a28c594
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

Loading…