Hydrochloric Acid → HCID 86651550, compound

HRID 1484910Notes

Reaction equation

[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([C:16]#[CH:17])=[CH:14][N:13]=[C:12]([C:18]4[S:22][C:21]([CH2:23][NH:24]C(=O)OC(C)(C)C)=[CH:20][CH:19]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[ClH:32]>CCO>[ClH:32].[NH2:24][CH2:23][C:21]1[S:22][C:18]([C:12]2[N:11]=[C:10]([NH:9][C:6]3[CH:5]=[C:4]([CH:1]4[CH2:2][CH2:3]4)[NH:8][N:7]=3)[C:15]([C:16]#[CH:17])=[CH:14][N:13]=2)=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of tert-butyl (5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-ethynylpyrimidin-2-yl)thiophen-2-yl)methylcarbamate (Compound 168) (100 mg, 0.23 mmol, 1.0 equiv.) in EtOH (3 mL) was added HCl(g)/EtOH (saturated, 3 mL). After stirred at 20° C. for 12 h, the reaction mixture was concentrated in vacuum. The crude product was crystallized with THF/isopropyl to afford 2-(5-(aminomethyl)thiophen-2-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-ethynylpyrimidin-4-amine hydrochloride (Compound 167) (41.4 mg, 20.9%, two steps). LC-MS (m/z)=337.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.80-0.84 (m, 2H), 1.00-1.05 (m, 2H), 2.01-2.04 (m, 1H), 4.28 (d, J=5.2 Hz, 2H), 4.92 (s, 1H), 6.52 (s, 1H), 7.38 (d, J=3.6 Hz, 1H), 7.87 (d, J=4.0 Hz, 1H), 8.53 (s, 1H), 8.65 (bs, 2H), 9.13 (s, 1H).

Workup

concentrationthe reaction mixture was concentrated in vacuum
customThe crude product was crystallized with THF/isopropyl

Sources & evidence

ORD record: ord-14159d5a8daa4c22996107c438392f04
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Reaction notes

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