Ethanol → HCID 56848548, compound

HRID 625810Notes

Reaction equation

[NH2:1][CH:2]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.C[CH2:28][OH:29]>C(OCC)=O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH:2]([C:3]2[N:12]=[C:11]([NH:13][C:14]3[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=3)[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=2)[NH:1][CH:28]=[O:29])=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To 2-(amino(4-fluorophenyl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine from Example 45 Step B (0.1 g, 0.28 mmol) in ethyl formate (4 mL) were added TEA (0.2 mL) and EtOH (0.5 mL), and the mixture was heated to 120° C. for 30 min in a Biotage microwave reactor and then concentrated under reduced pressure. The residue was diluted with DMSO (5 mL) and purified by reverse-phase preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% HOAC/MeOH and solvent A=0.05% HOAc/H2O) to afford N-((4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methyl)formamide (8 mg, 8%). 1H NMR (300 MHz, DMSO-d6) δ 2.26 (s, 3H) 6.07 (d, 1H) 6.44 (s, 1H) 7.16 (t, 2H) 7.4-7.6 (m, 3H) 7.8 (m, 2H) 8.21 (s, 1H) 8.62 (d, 1H) 9.06 (d, 1H) 10.48 (bs, 1H) 12.17 (bs, 1H); LC-MS (ESI) m/z 377 (M+H)+.

Workup

concentrationconcentrated under reduced pressure
additionThe residue was diluted with DMSO (5 mL)
custompurified by reverse-phase preparative HPLC (Varian diphenyl reverse phase column
washeluted with gradient of solvent B=0.05% HOAC/MeOH and solvent A=0.05% HOAc/H2O)

Sources & evidence

ORD record: ord-57b3430928b6493e999c0f3a2724d013
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09308207B2

Reaction notes

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