Acetic Acid → 5-(6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 1887593Notes

Reaction equation

HRID 1887593 reaction equation
[N:1]1[C:6]2[CH2:7][NH:8][CH2:9][C:5]=2[C:4]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)=[O:21])[CH:15]=[CH:14]3)=[N:3][CH:2]=1.C=O.[C:35](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O.[Cl-].[Na+].O.C(Cl)Cl>[F:32][C:29]([F:31])([F:30])[C:25]1[CH:24]=[C:23]([NH:22][C:20]([N:16]2[C:17]3[C:13](=[CH:12][C:11]([O:10][C:4]4[C:5]5[CH2:9][N:8]([CH3:35])[CH2:7][C:6]=5[N:1]=[CH:2][N:3]=4)=[CH:19][CH:18]=3)[CH:14]=[CH:15]2)=[O:21])[CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 593944295-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Product 1

HCID 593945975-(6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide (140 mg, 0.320 mmol) is suspended in 1,2-dichloroethane (5 mL), and formaldehyde (50 μl, 0.672 mmol) and acetic acid (36 μl, 0.629 mmol) and sodium triacetoxyborohydride (139 mg, 0.656 mmol) are added and the mixture heated to 60° C. overnight. The reaction is cooled to rt, diluted with water, brine and DCM. The organic phase is removed, dried, and concentrated to an oil that is purified via FCC (0-10% NH3/MeOH:DCM) to obtain 5-(6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 454.95 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.38 (s, 1H), 8.56 (s, 1H), 8.27 (d, J=9.09 Hz, 1H), 8.09-8.13 (m, 2H), 7.96 (s, 1H), 7.65 (t, J=8.08 Hz, 1H), 7.48-7.51 (m, 2H,) 7.15 (dd, J=8.97, 2.40 Hz, 1H), 6.80 (d, J=3.79 Hz, 1H), 3.91 (s, 4H), 2.52 (s, 3H).

Workup

  1. temperatureThe reaction is cooled to rt
  2. customThe organic phase is removed
  3. customdried
  4. concentrationconcentrated to an oil that
  5. customis purified via FCC (0-10% NH3/MeOH:DCM)

Sources & evidence

ORD record
ord-82c6ffda433d41efb852426f55a17b20
Source dataset
uspto-grants-2013_08
Patent number
US08501756B2

Reaction notes

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