D-Lactic Acid → HCID 178462364, compound

HRID 711964Notes

Reaction equation

HRID 711964 reaction equation
[NH2:1][C:2]1[C:3]([NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([CH2:18][CH2:19][C:20]#[N:21])[CH2:14][CH2:13]2)=[C:4]2[S:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[OH:22][C@H:23]([CH3:27])[C:24](O)=[O:25].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>C(Cl)Cl>[C:20]([CH2:19][CH2:18][C@H:15]1[CH2:14][CH2:13][C@H:12]([NH:11][C:3]2[C:2]([NH:1][C:24](=[O:25])[C@H:23]([OH:22])[CH3:27])=[CH:7][N:6]=[C:5]3[CH:8]=[CH:9][S:10][C:4]=23)[CH2:17][CH2:16]1)#[N:21]

Participants

6

Reactant 4

HCID 61503D-Lactic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178511026HCID 178511026, compound

Product 1

HCID 178462364HCID 178462364, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-{trans-4-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]cyclohexyl}propanenitrile (0.048 g, 0.16 mmol) and (R)-2-hydroxypropanoic acid (0.019 g, 0.21 mmol) in methylene chloride (0.96 mL) was added N,N-diisopropylethylamine (60 μL, 0.35 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (66 mg, 0.17 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was washed with water. The organic layers were concentrated and purified on silica gel (eluting with 0 to 10% MeOH in dichloromethane) to give (2R)—N-(7-{[trans-4-(2-Cyanoethyl)cyclohexyl]amino}thieno[3,2-b]pyridin-6-yl)-2-hydroxypropanamide. LCMS calculated for C19H25N4O2S (M+H)+: m/z=373.2. Found: 373.0. A solution of the amide intermediate in acetic acid (0.3 mL) was stirred at 105° C. for 5 h. The solvent in the reaction mixture was removed in vacuo, diluted with MeOH and purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (6 mg, 10%). LCMS calculated for C19H23N4OS (M+H)+: m/z=355.2. Found: 355.1.

Workup

  1. washThe mixture was washed with water
  2. concentrationThe organic layers were concentrated
  3. custompurified on silica gel (eluting with 0 to 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-31d843cb87db4c3489b81c1bb68c18ab
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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