Aminoacetonitrile → ethyl 4-(3-(cyanomethylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882131Notes

Reaction equation

HRID 882131 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13]([C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([OH:20])=O)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2].[NH2:24][CH2:25][C:26]#[N:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:25]([CH2:26][NH:27][C:18]([C:17]1[CH:16]=[C:15]([C:13]2[C:14]3[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][NH:8][C:9]=3[N:10]=[CH:11][N:12]=2)[CH:23]=[CH:22][CH:21]=1)=[O:20])#[N:24]

Participants

7

Reactant 4

HCID 10901AminoacetonitrileHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896298643-(5-(ethoxycarbonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzoic acid

Product 1

HCID 89629991ethyl 4-(3-(cyanomethylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of crude 3-(5-(ethoxycarbonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzoic acid 113 mg (theoretical mass 55 mg, 0.18 mmol), 2-aminoacetonitrile (49.5 mg, 0.883 mmol), HATU (101 mg, 0.265 mmol) in DMF (1.0 mL) was added DIPEA (62 μL, 0.35 mmol). The reaction mixture was heated to 45° C. for 2 hours and then diluted with ethyl acetate (5 mL). The reaction mixture was washed with 2 M aqueous sodium bicarbonate (5 mL) and brine (5 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier to give ethyl 4-(3-(cyanomethylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C18H16N5O3[M+H]+: 350, found 350. 1H NMR (600 MHz, DMSO-D6) δ 9.19 (t, J=5.28 Hz 1H), 8.55 (s, 1H), 8.20 (s, 1H), 8.12 (s, 1H), 7.86 (d, J=8.21 Hz, 1H), 7.75 (d, J=7.63 Hz, 1H), 7.48 (t, J=7.63 Hz, 1H), 6.86 (bs, 1H), 4.30 (q, J=5.28 Hz, 2H), 3.76 (q, J=7.04 Hz, 2H), 0.83 (t, J=7.04 Hz, 3H).

Workup

  1. washThe reaction mixture was washed with 2 M aqueous sodium bicarbonate (5 mL) and brine (5 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-eb5fb86705ac45ed8cea2a87639df467
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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