Diisopropylethylamine → 4-Amino-6-[(S)-1-(5-fluoro-6,7,8,9-tetrahydro-2,9a-diazabenzo[cd]azulen-1-yl)ethylamino]pyrimidine-5-carbonitrile

HRID 243480Notes

Reaction equation

[F:1][C:2]1[CH2:11][CH2:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]([C@@H:15]([NH2:17])[CH3:16])=[N:13][CH:14]=[C:4]([C:5]=23)[CH:3]=1.[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23](Cl)[N:22]=[CH:21][N:20]=1.CCN(C(C)C)C(C)C>C(O)(C)C>[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([NH:17][C@H:15]([C:12]2[N:6]3[CH2:7][CH2:8][C:9]4[CH2:10][CH2:11][C:2]([F:1])=[CH:3][C:4]([C:5]=43)=[CH:14][N:13]=2)[CH3:16])[N:22]=[CH:21][N:20]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-(5-fluoro-6,7,8,9-tetrahydro-2,9a-diazabenzo[cd]azulen-1-yl)ethylamine (70 mg, 0.30 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (46.4 mg, 0.30 mmol), and DIPEA (102 μL, 0.60 mmol) in isopropanol (1.5 mL) was stirred at 90° C. for 3 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 2-7% 2M NH3/MeOH in DCM). Crystallisation from MeOH (5 mL) afforded 406 as a white solid (43.2 mg, 41%). LCMS (Method K): RT 2.91 min [M+H]+ 352.1. 1H NMR ((CD3)2SO, 400 MHz): 8.07 (1H, s), 7.69 (1H, d, J=7.5 Hz), 7.45 (1H, dd, J=8.8, 4.8 Hz), 7.31 (2H, bs), 7.00 (1H, dd, J=10.8, 8.7 Hz), 5.67 (1H, quintet, J=6.9 Hz), 4.25-4.14 (2H, m), 3.05-3.01 (2H, m), 2.08-1.93 (4H, m), 1.58 (3H, d, J=6.7 Hz)

Workup

temperatureAfter cooling to RT
customvolatiles were removed under reduced pressure
customthe resulting residue was purified by column chromatography (Si—PCC, gradient 2-7% 2M NH3/MeOH in DCM)
customCrystallisation from MeOH (5 mL)

Sources & evidence

ORD record: ord-47d221edf1564dbf935c5cd135f30eca
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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