Formaldehyde → HCID 68657022, compound

HRID 1020565Notes

Reaction equation

HRID 1020565 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][N:13]([C:16]3[CH:24]=[C:23]4[C:19]([C:20]5[CH2:29][CH2:28][NH:27][CH2:26][C:21]=5[N:22]4[CH3:25])=[CH:18][CH:17]=3)[C:12](=[O:30])[CH:11]=2)=[N:6][CH:7]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:35](C)=O.[Na+].C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:59].Cl>C(Cl)Cl.CO>[ClH:1].[ClH:59].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][N:13]([C:16]3[CH:24]=[C:23]4[C:19]([C:20]5[CH2:29][CH2:28][N:27]([CH3:35])[CH2:26][C:21]=5[N:22]4[CH3:25])=[CH:18][CH:17]=3)[C:12](=[O:30])[CH:11]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 57950305HCID 57950305, compound

Product 1

HCID 68657022HCID 68657022, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-((5-Chloropyridin-2-yl)methoxy)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one (80 mg, 0.19 mmol) was dissolved a mixture of MeOH (3 mL) and CH2Cl2 (1 mL) and formaldehyde (9.0 mg, 0.29 mmol, 37% aqueous solution) was added. After stirring for 45 minutes, NaBH(OAc)3 (80 mg, 0.38 mmol) was added and the reaction mixture was stirred for a further 10 minutes. The mixture was diluted with CH2Cl2, washed with saturated Na2CO3 solution and concentrated to provide the free base. Conversion to the dihydrochloride salt using the procedure of Example 30 (step g) provided the title compound (83 mg, 86%) as an orange solid: mp 202-210° C.; 1H NMR (500 MHz, CD3OD) δ 8.68 (br s, 1H), 8.05 (dd, J=8.0, 2.4 Hz, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.65 (d, J=8.3 Hz, 1H), 7.51 (d, J=1.6 Hz, 1H), 7.09 (dd, J=8.3, 1.8 Hz, 1H), 6.53 (dd, J=7.6, 1.7 Hz, 1H), 6.28 (d, J=1.6 Hz, 1H), 5.36 (s, 2H), 4.85-4.80 (m, 1H), 4.49 (d, J=15.3 Hz, 1H), 3.89-3.84 (m, 1H), 3.72 (s, 3H), 3.53-3.47 (m, 1H), 3.22-3.19 (m, 2H), 3.16 (s, 3H); ESI MS m/z 435 [M+H]+; HPLC (Method B) 97.8% (AUC), tR=12.2 min.

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred for a further 10 minutes
  3. washwashed with saturated Na2CO3 solution
  4. concentrationconcentrated
  5. customto provide the free base

Sources & evidence

ORD record
ord-7896684d5c8a48158820f0427f5b97e4
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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