Dimethylformamide → HCID 71015337, compound

HRID 2207525Notes

Reaction equation

HRID 2207525 reaction equation
[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

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71015333HCID 71015333, compound

Product 1

HCID 71015337HCID 71015337, compound

Procedure

A mixture of (E/Z)-3-cyclopropyl-2-(trifluoromethyl)acrylic acid (30 mg, 0.17 mmol), (R)-3-(4-phenoxyphenyl)-1-(pyrrolidin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (158 mg, 0.52 mmol), Triethylamine (18.2 mg, 0.18 mmol) and DMF (3 mL) were stirred at room temperature for 10 min. O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (69 mg, 0.18 mmol) was added and the reaction mixture was stirred for 2 h. The solvent was evaporated and the oil was worked up with ethylacetate and water. The organic layer was washed with brine and dried over 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: 549 (M+1).

Workup

  1. stirringthe reaction mixture was stirred for 2 h
  2. customThe solvent was evaporated
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customPurification with column chromatography (SiO2, MeOH|DCM with gradient form 1% to 2% in total 500 mL)

Sources & evidence

ORD record
ord-781d3af9dc204b3bab01d624ad6f67c2
Source dataset
uspto-grants-2016_06
Patent number
US09376438B2

Reaction notes

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