Triethylamine → N-(5-(3-(3-(2-cyanopropan-2-yl)phenyl)ureido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184851Notes

Reaction equation

[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)C(O)=O)([CH3:5])[CH3:4])#[N:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:22])C=CC=CC=1.C([N:34]([CH2:37]C)CC)C.Cl.[NH2:40][C:41]1[CH:42]=[CH:43][C:44]([CH3:59])=[C:45]([NH:47][C:48]([C:50]2[S:58][C:53]3=[N:54][CH:55]=[CH:56][N:57]=[C:52]3[CH:51]=2)=[O:49])[CH:46]=1>C1(C)C=CC=CC=1.C1COCC1>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([NH:34][C:37](=[O:22])[NH:40][C:41]2[CH:42]=[CH:43][C:44]([CH3:59])=[C:45]([NH:47][C:48]([C:50]3[S:58][C:53]4=[N:54][CH:55]=[CH:56][N:57]=[C:52]4[CH:51]=3)=[O:49])[CH:46]=2)[CH:12]=[CH:13][CH:14]=1)([CH3:4])[CH3:5])#[N:2]

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 3-(2-cyanopropan-2-yl)benzoic acid 3 (50 mg, 0.264 mmol), diphenylphosphoryl azide (0.074 mL, 95 mg, 0.344 mmol) and triethylamine (0.110 mL, 0.793 mmol) in toluene (1 mL) was stirred at 100° C. for 1 h. N-(5-amino-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide hydrochloride 29 (85 mg, 0.264 mmol) in THF (1 mL) was added and stirred at 90° C. for 1 h. Evaporated to dryness and purified by chromatography (0-50% EtOAc in CH2Cl2) to yield the title compound N-(5-(3-(3-(2-cyanopropan-2-yl)phenyl)ureido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 40 (88 mg, 70.8%). NMR (400 MHz, DMSO) 2.21 (s, 3H), 7.11 (m, 1H), 7.23 (m, 2H), 7.33 (t, J=7.8 Hz, 1H), 7.40 (m, 1H), 7.63 (d, J=1.9 Hz, 1H), 7.69 (t, J=1.9 Hz, 1H), 8.53 (s, 1H), 8.73 (s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.83 (s, 1H), 8.88 (d, J=2.3 Hz, 1H), 10.47 (s, 1H). (m/z)=471 (M+H)+.

Workup

customEvaporated to dryness
custompurified by chromatography (0-50% EtOAc in CH2Cl2)

Sources & evidence

ORD record: ord-cd0b505cc552418b9e4fd7b631336615
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669256B2

Reaction notes

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