D-Lactic Acid → HCID 25001555, compound

HRID 2239506Notes

Reaction equation

HRID 2239506 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:26][CH3:27])=[C:17]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH:18]=2)[N:13]=[N:12][C:11]=1[C:28]([NH2:30])=[O:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[OH:64][C@H:65]([CH3:69])[C:66](O)=[O:67].C(N(C(C)C)C(C)C)C>C(Cl)Cl.CO.O>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:26][CH3:27])=[C:17]([N:20]3[CH2:21][CH2:22][N:23]([C:66](=[O:67])[C@H:65]([OH:64])[CH3:69])[CH2:24][CH2:25]3)[CH:18]=2)[N:13]=[N:12][C:11]=1[C:28]([NH2:30])=[O:29]

Participants

8

Reactant 4

HCID 61503D-Lactic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOP2×HCID 67083896HCID 67083896, compound

Product 1

HCID 25001555HCID 25001555, compoundYield 37.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-fluoro-4-methylphenylamino)-7-methoxy-6-(piperazin-1-yl)cinnoline-3-carboxamide (Example 46, 0.395 g, 0.96 mmol) in CH2Cl2 (20 mL) and MeOH (5 mL) was added benzotriazol-1-yloxytripyrrolidino-phosphonium hexafluorophosphate (0.551 g, 1.06 mmol), (R)-2-hydroxypropanoic acid (0.079 mL, 1.06 mmol), and N-ethyldiisopropylamine (0.181 mL, 1.06 mmol). After 1 hour, an additional portion of benzotriazol-1-yloxytripyrrolidino-phosphonium hexafluorophosphate (1.10 g, 2.12 mmol) was added. After 2 hours, water (100 mL) was added, and the mixture extracted with CH2Cl2. The organic extract was concentrated under reduced pressure, and the residue purified with silica chromatography (Hex/EtOAc, then with CH2Cl2/MeOH). The crude product was triturated with CH3CN and filtered to give 173 mg (37%) yellow solid. 1H NMR: 11.33 (s, 1H), 8.77 (s, 1H), 7.91 (s, 1H), 7.60 (s, 1H), 7.17 (m, 2H), 7.06 (m, 1H), 6.62 (s, 1H), 4.98 (d, 1H), 4.39 (m, 1H), 4.01 (s, 3H), 3.54 (m, 4H), 2.72 (m, 4H), 2.32 (s, 3H), 1.16 (d, 3H); m/z 484.

Workup

  1. waitAfter 2 hours
  2. extractionthe mixture extracted with CH2Cl2
  3. extractionThe organic extract
  4. concentrationwas concentrated under reduced pressure
  5. customthe residue purified with silica chromatography (Hex/EtOAc
  6. customThe crude product was triturated with CH3CN
  7. filtrationfiltered

Sources & evidence

ORD record
ord-fd12efdb2469426ea3a0ee5118e9b15e
Source dataset
uspto-grants-2010_05
Patent number
US07723337B2

Reaction notes

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