Sodium Carbonate → HCID 118045775, compound

HRID 595890Notes

Reaction equation

[NH2:1][C:2]1[N:3]=[CH:4][C:5]([CH2:9][CH:10]([OH:12])[CH3:11])=[N:6][C:7]=1Br.[CH2:13]([NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][C:24]=1[F:32])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:1][C:2]1[C:7]([C:26]2[CH:27]=[CH:28][C:23]([C:21]([NH:20][CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[O:22])=[C:24]([F:32])[CH:25]=2)=[N:6][C:5]([CH2:9][CH:10]([OH:12])[CH3:11])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (+/−)-1-(5-amino-6-bromopyrazin-2-yl)propan-2-ol (30 mg, 0.129 mmol) in DME (970 μL) was added 4-(benzylcarbamoyl)-3-fluorophenylboronic acid (31.8 mg, 0.116 mmol), PdCl2(dppf)CH2Cl2 adduct (10.56 mg, 0.013 mmol), 2M Na2CO3 (323 μL). The reaction mixture was stirred at 120° C. for 10 min in microwave. The reaction mixture was partitioned between EtOAc and water. the organic was dried and concentrated. the crude product was purified by Prep HPLC. The pure fraction was combined and desalt to yield (+/−)-4-(3-amino-6-(2-hydroxypropyl)pyrazin-2-yl)-N-benzyl-2-fluorobenzamide. LCMS (m/z): 381.2 (MH+), 0.67 min; 1H NMR (400 MHz, CD3OD) δ ppm 7.95-7.81 (m, 2H), 7.66 (dd, J=1.6, 8.2 Hz, 1H), 7.58 (dd, J=1.6, 11.7 Hz, 1H), 7.43-7.31 (m, 4H), 7.31-7.19 (m, 1H), 4.62 (s, 2H), 4.16-4.04 (m, 1H), 2.79 (d, J=6.3 Hz, 2H), 1.23 (d, J=6.3 Hz, 3H).

Workup

customThe reaction mixture was partitioned between EtOAc and water
customthe organic was dried
concentrationconcentrated
customthe crude product was purified by Prep HPLC

Sources & evidence

ORD record: ord-448298e35f544fb195d49a9315ec8919
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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