Acetone → HCID 44196978, compound

HRID 521362Notes

Reaction equation

HRID 521362 reaction equation
[CH3:1][C:2]([CH3:4])=O.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:15]2[C:23]3[C:18](=[CH:19][C:20]([C:24]4[C:25]5[C@H:32]([CH3:33])[CH2:31][CH2:30][C:26]=5[N:27]=[CH:28][N:29]=4)=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:13][NH2:14])=[CH:8][CH:7]=1.C(N(CC)C(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C@H:12]([C:15]2[C:23]3[C:18](=[CH:19][C:20]([C:24]4[C:25]5[C@H:32]([CH3:33])[CH2:31][CH2:30][C:26]=5[N:27]=[CH:28][N:29]=4)=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:13][NH:14][CH:2]([CH3:4])[CH3:1])=[CH:8][CH:7]=1

Participants

7

Reactant 5

HCID 180AcetoneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 67437085HCID 67437085, compound

Product 1

HCID 44196978HCID 44196978, compoundYield 16.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetone (0.0195 mL, 0.266 mmol) was added to a solution of 2-(4-chlorophenyl)-2-(6-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1H-indol-3-yl)ethanamine (107 mg, 0.266 mmol) and N,N-diisopropylethylamine (0.139 mL, 0.797 mmol) in methylene chloride (2.0 mL). The reaction mixture was stirred for 10 minutes, and then sodium triacetoxyborohydride (0.0188 g, 0.0885 mmol) was added. After stirring for 2.5 hours, saturated NaHCO3 was added, and the mixture was stirred vigorously 10 minutes. The mixture was extracted with DCM (3×10 mL). The combined organic were dried (Na2SO4), filtered and concentrated. The crude product was purified by SFC chiral chromatography (Chiral OJH (21.2×250 mm) 25% methanol+0.1% TEA) to give N-((R)-2-(4-chlorophenyl)-2-(6-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1H-indol-3-yl)ethyl)propan-2-amine (19.8 mg, 16.8%) as the first peak. LCMS: M+1 445.3. 1H NMR (CDCl3, 400 MHz) δ 11.16 (s, 1H), 8.93 (s, 1H), 7.93 (s, 1H), 7.49-7.46 (m, 3H), 7.38 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.5 Hz, 2H), 4.36 (t, 1H), 3.89 (m, 1H), 3.23 (m, 1H), 3.14-2.99 (m, 2H), 2.94-2.86 (m, 1H), 2.77 (m, 1H), 2.34 (m, 1H), 1.68 (m, 1H), 0.96 (d, 6H), 0.92 (d, 3H).

Workup

  1. stirringAfter stirring for 2.5 hours
  2. stirringthe mixture was stirred vigorously 10 minutes
  3. extractionThe mixture was extracted with DCM (3×10 mL)
  4. dry with materialThe combined organic were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by SFC chiral chromatography (Chiral OJH (21.2×250 mm) 25% methanol+0.1% TEA)

Sources & evidence

ORD record
ord-7c7c8e2e78a54fcc967a31e2a1cf03e6
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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