Dimethylformamide → HCID 71015337、化合物

反応式

[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([CH2:24][C@H:25]3[CH2:29][CH2:28][CH2:27][NH:26]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.N1(OC(N(C)C)=[N+](C)C)[C:41]2N=[CH:43][CH:44]=[CH:45][C:40]=2N=N1.[F:54][P-](F)(F)(F)(F)F.CN([CH:64]=[O:65])C>>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([CH2:24][C@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3[C:64](=[O:65])[C:41]([F:54])=[CH:40][CH:45]3[CH2:43][CH2:44]3)[N:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:13][CH:12]=3)[C:22]=12

参加物

反応物 4

HCID 6228Dimethylformamide

HCID 8471Triethylamine

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

HCID 71015333HCID 71015333、化合物

生成物 1

HCID 71015337HCID 71015337、化合物

実験手順

A mixture of (E/Z)-3-cyclopropyl-2-fluoroacrylic acid (68 mg, 0.52 mmol), (R)-3-(4-phenoxyphenyl)-1-(pyrrolidin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (158 mg, 0.52 mmol), triethylamine (69 mg, 0.68 mmol) and DMF (4 mL) were stirred at room temperature for 10 mins. O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (257 mg, 0.68 mmol) was then added and the mixture was stirred for 75 min. The solvent was evaporated and the oil was worked up with ethylacetate and water. Organic layer was washed with brine and dried with MgSO4. Purification with column chromatography (SiO2, MeOH|DCM with gradient form 1% to 2% in total 500 mL) gave (R)-1-(2-((4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidin-1-yl)-3-cyclopropyl-2-fluoroprop-2-en-1-one. MS (pos. ion) m/z: 499 (M+1).