1,2-Dichloroethane → HCID 66678954, compound

HRID 1626637Notes

Reaction equation

HRID 1626637 reaction equation
Cl.[CH2:2]([NH:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH3:29])[C:17]3[CH2:22][NH:21][CH2:20][C:18]=3[N:19]=2)=[CH:10][C:9]=1[F:30])=[O:6])[CH3:3].CN1CCOCC1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:52]([N:55]1[CH2:60][CH2:59][CH:58]([C:61](O)=[O:62])[CH2:57][CH2:56]1)(=[O:54])[CH3:53]>CN(C=O)C>[C:52]([N:55]1[CH2:56][CH2:57][CH:58]([C:61]([N:21]2[CH2:22][C:17]3[C:16]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]4[CH3:29])=[N:15][C:14]([C:11]4[CH:12]=[CH:13][C:8]([NH:7][C:5]([NH:4][CH2:2][CH3:3])=[O:6])=[C:9]([F:30])[CH:10]=4)=[N:19][C:18]=3[CH2:20]2)=[O:62])[CH2:59][CH2:60]1)(=[O:54])[CH3:53]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1172551-Acetylpiperidine-4-carboxylic acidHCID 66687926HCID 66687926, compound2×

Product 1

HCID 66678954HCID 66678954, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of (S)-1-ethyl-3-(2-fluoro-4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (intermediate 18) (133 mg, 0.25 mmol) and N-methylmorpholine (55 μL, 0.5 mmol) in DMF (5 mL, anhydrous) was added EDC (53 mg, 0.275 mmol), HOBT (37 mg, 0.275 mmol), and 1-acetylpiperidine-4-carboxylic acid (43 mg, 0.25 mmol). The reaction mixture was stirred at room temperature until analysis by LCMS deemed reaction complete. Solvent was then removed in vacuo. Purified by prep. HPLC (low pH) Then further purified using a TsOH cartridge to remove residual formic acid from HPLC (loaded in MeOH eluted with 2M methanolic ammonia). Yielding a light pink solid (9.6 mg, 0.017 mmol, 7%).

Workup

  1. customreaction complete
  2. customSolvent was then removed in vacuo
  3. customPurified by prep
  4. customHPLC (low pH) Then further purified
  5. customto remove residual formic acid
  6. washfrom HPLC (loaded in MeOH eluted with 2M methanolic ammonia)

Sources & evidence

ORD record
ord-a698c6134c8440cea64ef032b23310e8
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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