Ethylenediamine → (3-[4-(5-Fluoro-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]-1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}azetidin-3-yl)acetonitrile

HRID 1617377Notes

Reaction equation

HRID 1617377 reaction equation
[F:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:15][C:16]1[C:17]([C:33]2[CH:34]=[N:35][N:36]([C:38]3([CH2:48][C:49]#[N:50])[CH2:41][N:40]([CH:42]4[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]4)[CH2:39]3)[CH:37]=2)=[C:18]2[CH:24]=[CH:23][N:22](COCC[Si](C)(C)C)[C:19]2=[N:20][CH:21]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.FC(F)(F)C(O)=O.C(N)CN>C(Cl)Cl>[F:15][C:16]1[C:17]([C:33]2[CH:34]=[N:35][N:36]([C:38]3([CH2:48][C:49]#[N:50])[CH2:41][N:40]([CH:42]4[CH2:43][CH2:44][N:45]([C:4](=[O:6])[C:3]5[CH:7]=[CH:8][N:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[C:2]=5[F:1])[CH2:46][CH2:47]4)[CH2:39]3)[CH:37]=2)=[C:18]2[CH:24]=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1

Participants

8

Reactant 6

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 265964893-Fluoro-2-(trifluoromethyl)isonicotinic acidHCID 67421534{3-[4-(5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]-1-piperidin-4-ylazetidin-3-yl}acetonitrile

Product 1

HCID 58431297(3-[4-(5-Fluoro-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]-1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}azetidin-3-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-fluoro-2-(trifluoromethyl)isonicotinic acid (70.0 mg, 0.335 mmol), {3-[4-(5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]-1-piperidin-4-ylazetidin-3-yl}acetonitrile.3[HCl] (207 mg, 0.335 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (148 mg, 0.335 mmol) and triethylamine (0.234 mL, 1.68 mmol) in methylene chloride (2 mL) was stirred at room temperature for 1 hour. To the mixture was added trifluoroacetic acid (2 mL, 20 mmol). The resulting solution was stirred at room temperature for 1 hour and concentrated. The residue was dissolved in methanol (2 mL) and ethylenediamine (0.5 mL, 7 mmol). After being stirred at room temperature for 2 hours, the mixture was purified by HPLC (method B) to give 11.2 mg of the title compound as a white solid. LC/MS found: 571.3 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 11.85 (brs, 1H), 8.65 (d, J=4.4 Hz, 1H), 8.59 (s, 1H), 8.23 (d, J=3.2 Hz, 1H), 8.20 (s, 1H), 7.89 (s, 1H), 7.61 (s, 1H), 6.85 (s, 1H), 4.04 (m,1H), 3.72 (m, 2H), 3.58 (m, 2H), 3.53 (m, 2H), 3.53 (m, 2H), 3.40 (m, 1H), 3.25 (m, 1H), 3.06 (t, J=9.2 Hz, 1H), 2.54 (m, 1H), 1.75 (m, 1H), 1.62 (m, 1H), 1.26 (m, 1H), 1.21 (m, 1H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in methanol (2 mL)
  3. stirringAfter being stirred at room temperature for 2 hours
  4. customthe mixture was purified by HPLC (method B)

Sources & evidence

ORD record
ord-ea8f60e485714c789f6ad7b4b1b2f2c8
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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