Tetrahydrofuran → HCID 58075806, compound

HRID 2370136Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.CC[N:21]([CH:25]([CH3:27])[CH3:26])C(C)C.[CH2:28]1COC[CH2:29]1>>[Cl:1][C:2]1[N:3]=[C:4]([NH:21][C@@H:25]([CH:26]2[CH2:29][CH2:28]2)[CH3:27])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1

Participants

Reactant 3

HCID 8028Tetrahydrofuran

HCID 81531Diisopropylethylamine

HCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 58075806HCID 58075806, compoundYield 63.1%

Conditions

Temperature: 60 °C

Procedure

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) (100 mg, 0.353 mmol) in THF (1766 μL) was added (R)-1-cyclopropylethanamine, HCl (172 mg, 1.413 mmol) and DIEA (493 μL, 2.83 mmol). The mixture was stirred at 60° C. for 5 days. The crude product was purified by Prep-HPLC get 2-chloro-N-((R)-1-cyclopropylethyl)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Haa) (74 mg, 0.223 mmol, 63.1% yield). LC-MS (M+H)+=332.3. 1H NMR (500 MHz, CDCl3) δ ppm 7.06-7.18 (m, 2 H) 7.00 (td, J=8.70, 1.53 Hz, 2 H) 4.65 (d, J=5.80 Hz, 1 H) 4.26 (t, J=7.17 Hz, 1 H) 3.63-3.79 (m, 1 H) 2.62-2.82 (m, 3 H) 2.04-2.16 (m, 1 H) 1.26-1.40 (m, 3 H) 0.94 (qd, J=8.24, 3.36 Hz, 1 H) 0.42-0.62 (m, 3 H) 0.24-0.40 (m, 1 H).

Workup

customThe crude product was purified by Prep-HPLC

Sources & evidence

ORD record: ord-5c7aa1b6c18842a585db2cb9672dfeb0
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710061B2

Reaction notes

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