Methyl DL-prolinate → HCID 78324583, compound

HRID 2170167Notes

Reaction equation

HRID 2170167 reaction equation
[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:32]=2)[C:29](O)=[O:30])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:57]1[CH2:61][CH2:60][CH2:59][CH:58]1[C:62]([O:64][CH3:65])=[O:63]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:32]=2)[C:29]([N:57]2[CH2:61][CH2:60][CH2:59][CH:58]2[C:62]([O:64][CH3:65])=[O:63])=[O:30])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 94239Methyl DL-prolinateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 78323978HCID 78323978, compound

Product 1

HCID 78324583HCID 78324583, compoundYield 59.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinic acid (80.0 mg, 0.190 mmol) (prepared as in Example 12) in DMF (2 mL), were added DMAP (35.0 mg, 0.285 mmol) and HATU (108 mg, 0.285 mmol) and the reaction mixture was stirred for 10 minutes. Methyl pyrrolidine-2-carboxylate (12.0 g, 0.0950 mmol) was added and the reaction mixture was stirred at room temperature for 14 h. The reaction mixture concentrated under reduced pressure to remove DMF and to the resulting residue water (10 mL) was added. The aqueous mixture was extracted with CH2Cl2 (15×2 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-68 as described in general methods) to obtain methyl 1-(5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinoyl)pyrrolidine-2-carboxylate (30.0 mg, 59.3%). LCMS Condition B-14: retention time 2.31 min, [M−1]=531.2. HPLC Condition B-63: retention time 16.30 min, Purity 99.70%. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.87-1.98/2.30-2.35 (m, 4H), 3.44/3.70 (s, 3H), 3.55/3.67 (dd, J=6.0 Hz, J=6.8 Hz, 2H), 4.47-4.49/4.56-4.58 (m, 1H), 4.54/4.82 (d, J=5.6 Hz, 2H), 6.71/6.76 (t, J=5.6 Hz, 1H), 6.82 (d, J=2.8 Hz, 1H), 7.23-7.56 (m, 10H), 7.91/7.94 (d, J=2.8 Hz, 1H), 8.44/8.58 (t, J=2.0 Hz, 1H), 8.65/8.81 (d, J=2.0 Hz, 1H), 9.39/9.44 (d, J=2.0 Hz, 1H). Molecule exists as two rotomers with ratio 70/30.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 14 h
  2. concentrationThe reaction mixture concentrated under reduced pressure
  3. customto remove DMF
  4. additionto the resulting residue water (10 mL) was added
  5. extractionThe aqueous mixture was extracted with CH2Cl2 (15×2 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC (Condition B-68 as described in general methods)

Sources & evidence

ORD record
ord-da98d7bfdccd45e9a85db34cc542a1b8
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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