Trifluoroacetic acid → HCID 86719390, compound

HRID 2175653Notes

Reaction equation

HRID 2175653 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([Cl:18])[N:8]([C@@H:19]3[CH2:23][CH2:22][N:21]([C:24](OC(C)(C)C)=[O:25])[CH2:20]3)[C:4]=2[N:5]=[CH:6][N:7]=1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.[CH:47]1([N:50]([CH3:57])[CH2:51]/[CH:52]=[CH:53]/C(O)=O)[CH2:49][CH2:48]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=3)=[C:9]([Cl:18])[N:8]([C@@H:19]3[CH2:23][CH2:22][N:21]([C:24](=[O:25])/[CH:53]=[CH:52]/[CH2:51][N:50]([CH:47]4[CH2:49][CH2:48]4)[CH3:57])[CH2:20]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 62344125HCID 62344125, compoundHCID 86719391HCID 86719391, compound

Product 1

HCID 86719390HCID 86719390, compoundYield 7.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-tert-butyl 3-(4-amino-6-chloro-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (37) (made according to procedures described in examples 1 and 2, using 4-chlorophenylboronic acid) (70 mg, 0.16 mmol) in DCM (4.0 mL) was added TFA (1 mL). The resulting mixture was stirred at r.t. for 1 hr before concentrated down to dryness under reduced pressure. The residue was dissolved in DMF (3 mL) and DIPEA (0.08 mL, 0.49 mmol), (E)-4-(cyclopropyl(methyl)amino)but-2-enoic acid (100 mg, 0.31 mmol), HBTU (60.4 mg, 0.16 mmol) were added, respectively. The resulting mixture was stirred at r.t. for 30 min. The solvents were evaporated. The crude product was directly purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3H2O)) to afford (R,E)-1-(3-(4-amino-6-chloro-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)-4-(cyclopropyl(methyl)amino)but-2-en-1-one (38) (6.0 mg, 7.9% yield) as a white solid. LC-MS (ESI): m/z (M/M+2) 486.4/488.4. 1H NMR (400 MHz, DMSO) δ 8.17-8.12 (m, 1H), 7.56 (dd, J=8.4, 1.6 Hz, 2H), 7.48-7.40 (m, 2H), 6.77-6.60 (m, 1H), 6.37 (m, 1H), 6.10 (br, 1H), 5.49-5.28 (m, 1H), 4.24 (t, J=9.1 Hz, 1H), 4.17-3.93 (m, 1H), 3.91-3.75 (m, 1H), 3.69-3.53 (m, 1H), 3.05-2.59 (m, 3H), 2.38-2.27 (m, 1H), 2.20 (d, J=16.0 Hz, 3H), 1.82-1.46 (m, 1H), 0.48-0.36 (m, 2H), 0.32-0.18 (m, 2H).

Workup

  1. concentrationbefore concentrated down to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in DMF (3 mL)
  3. stirringThe resulting mixture was stirred at r.t. for 30 min
  4. customThe solvents were evaporated
  5. customThe crude product was directly purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3H2O))

Sources & evidence

ORD record
ord-0cc716bfa2f1460ca2eeea457d47195c
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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