Triethylamine → HCID 86706462, compound

HRID 919592Notes

Reaction equation

HRID 919592 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[C:6]([F:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH:36]1[CH2:41][CH2:40][CH2:39][C@H:38]([O:42][C:43]2[C:44]3[CH:51]=[CH:50][NH:49][C:45]=3[N:46]=[CH:47][N:48]=2)[CH2:37]1.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[N:46]1[C:45]2[NH:49][CH:50]=[CH:51][C:44]=2[C:43]([O:42][C@H:38]2[CH2:39][CH2:40][CH2:41][N:36]([C:11](=[O:13])[CH2:10][NH:9][C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH2:37]2)=[N:48][CH:47]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67515603HCID 67515603, compoundHCID 86706459HCID 86706459, compound

Product 1

HCID 86706462HCID 86706462, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled solution of 2-(3-chloro-5-fluorophenylamino)acetic acid (139 mg, 0.68 mmol) at 0° C. in DMF (5 mL) was added HOBt (136 mg, 0.10 mmol), EDCI (197 mg, 0.10 mmol), (S)-4-(piperidin-3-yloxy)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (150 mg, 0.7 mmol) and Et3N (0.2 mL, 1.37 mmol) at 0° C. The reaction mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was diluted with EtOAc (50 mL) and washed with water (3×20 mL). The combined EtOAc layer was dried over Na2SO4 and concentrated in vacuo to give a residue that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford (45 mg, 17%) the titled compound. 1H NMR (400 MHz, DMSO-d6): δ 12.08 and 12.05 (2s, 1H), 8.41 and 8.39 (2s, 1H), 7.35 (s, 1H), 6.62-6.25 (m, 4H), 5.39-5.24 (m, 1H), 4.05-3.62 (m, 5H), 3.55-3.42 (m, 2H), 1.89-1.45 (m, 4H). LC-MS: m/z [M+1]=404.

Workup

  1. washwashed with water (3×20 mL)
  2. dry with materialThe combined EtOAc layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto give a residue that
  5. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-349af566a9a74caca4e27456eec1a82d
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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