Acetic Acid → HCID 136186312, compound

HRID 1968108Notes

Reaction equation

HRID 1968108 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[CH:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:5]([C:6]=23)=[N:4][NH:3]1.C(O)(=O)C.[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.[BH4-].[Na+]>C(Cl)Cl>[C:15]1([CH:14]2[C:5]3=[N:4][NH:3][C:2](=[O:1])[C:11]4[CH:10]=[CH:9][CH:8]=[C:7]([C:6]=43)[NH:12][CH:13]2[C:21]2[CH:28]=[CH:27][C:24]([CH2:25][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:23][CH:22]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 136344752HCID 136344752, compound

Product 1

HCID 136186312HCID 136186312, compoundYield 14.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(3-oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (367 mg, 1 mmol) in dry DCM (15 mL) was added acetic acid (0.2 mL) followed by pyrrolidine (213 mg, 3 mmol). After the addition, the mixture was stirred at room temperature overnight. Then sodium borohydride (318 mg, 1.5 mmol) was added at 0° C. After the addition, the mixture was stirred at this temperature for 12 hr. DCM was removed under reduced pressure. The residue was washed with ethyl acetate/methanol (10/1) and filtered. The filtrate was concentrated to give the crude product, which was purified by prep-HPLC to give the title compound (62 mg, yield 14%) as white solid. LC-MS (ESI) m/z: 423 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 1.82-1.85 (m, 2H), 1.97 (s, 2H), 3.01-3.05 (m, 2H), 3.26 (d, 2H), 4.27 (d, 2H), 4.36 (d, 1H), 4.84 (d, 1H), 7.13-7.23 (m, 6H), 7.36-7.40 (m, 5H), 7.48 (s, 1H), 7.57-7.61 (t, 1H), 12.18 (s, 1H).

Workup

  1. additionAfter the addition
  2. additionAfter the addition
  3. stirringthe mixture was stirred at this temperature for 12 hr
  4. customDCM was removed under reduced pressure
  5. washThe residue was washed with ethyl acetate/methanol (10/1)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customto give the crude product, which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-9e235aa606f048908496e275c4676d68
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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