N-methyl-2-pyrrolidone → HCID 67439407, compound

HRID 340130Notes

Reaction equation

HRID 340130 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:12]2[N:16]3[CH2:17][CH2:18][NH:19][CH2:20][C:15]3=[N:14][N:13]=2)[NH2:11])=[CH:6][CH:5]=1.[N+](C1C=CC(C([O:30][C@H:31]2[C:35]3[N:36]=[CH:37][N:38]=[C:39]([Cl:40])[C:34]=3[C@H:33]([CH3:41])[CH2:32]2)=O)=CC=1)([O-])=O.CCN(C(C)C)C(C)C.CN1C(=O)CCC1.[OH-].[Na+]>CO>[ClH:3].[ClH:40].[NH2:11][CH:10]([C:7]1[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=1)[C:12]1[N:16]2[CH2:17][CH2:18][N:19]([C:39]3[C:34]4[C@H:33]([CH3:41])[CH2:32][C@@H:31]([OH:30])[C:35]=4[N:36]=[CH:37][N:38]=3)[CH2:20][C:15]2=[N:14][N:13]=1

Participants

7

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 67436165HCID 67436165, compoundHCID 86651804(5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

Product 1

HCID 67439407HCID 67439407, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (4-chlorophenyl)(5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)methanamine bishydrochloride (50 mg, 0.149 mmol), (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (49.8 mg, 0.149 mmol) and DIEA (0.130 mL, 0.745 mmol) in NMP (0.30 mL, 0.149 mmol) was heated at 100° C. for 1 day. The crude reaction mixture was diluted with methanol and filtered. The filtrate was purified (C18, 5-95% MeCN/H2O+1% TFA). The fractions containing product were isolated by basifying with 25% NaOH and extracting into CH2Cl2/isopropanol (3:1). The organic layers were concentrated, and the residue was diluted with methanol. The solution was saturated with HCl (g). The solution was evaporated to give (5R,7R)-4-(3-(Amino(4-chlorophenyl)methyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol bishydrochloride (15.3 mg, 25%). LCMS (APCI+) rt=2.28 min. 1H NMR (400 MHz, d6-DMSO+3 drops D2O) δ 8.83 (d, J=7.8 Hz, 1H), 7.55 (s, 4H), 6.02 (d, J=8.6 Hz, 1H), 5.30 (m, 1H), 4.54 (m, 1H), 4.36 (m, 1H), 4.24 (m, 1H), 4.09 (m, 1H), 3.48 (m, 1H), 2.21 (m, 1H), 2.08 (m, 1H), 1.26 (m, 1H), 1.19 (m, 3H).

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered
  3. customThe filtrate was purified (C18, 5-95% MeCN/H2O+1% TFA)
  4. additionThe fractions containing product
  5. customwere isolated
  6. extractionextracting into CH2Cl2/isopropanol (3:1)
  7. concentrationThe organic layers were concentrated
  8. additionthe residue was diluted with methanol
  9. customThe solution was evaporated

Sources & evidence

ORD record
ord-644338c6f8064f408e30ed62a0c2d167
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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