Acetone → N-((1'-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methyl)propan-2-amine

HRID 529146ノート

反応式

HRID 529146 の反応式
F[C:2](F)(F)[C:3](O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[CH2:22]([N:29]1[CH2:34][CH2:33][C:32]2([C:42]3[C:37](=[CH:38][CH:39]=[CH:40][C:41]=3[CH2:43][NH2:44])[N:36]([C:45]3[C:46]4[CH:53](CC)[CH2:52][CH2:51][C:47]=4[N:48]=[CH:49][N:50]=3)[CH2:35]2)[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH3:56][C:57]([CH3:59])=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(N)(C)C>ClCCCl>[CH2:22]([N:29]1[CH2:34][CH2:33][C:32]2([C:42]3[C:37](=[CH:38][CH:39]=[CH:40][C:41]=3[CH2:43][NH:44][CH:57]([CH3:59])[CH3:56])[N:36]([C:45]3[C:46]4[CH:53]([CH2:2][CH3:3])[CH2:52][CH2:51][C:47]=4[N:48]=[CH:49][N:50]=3)[CH2:35]2)[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

参加物

6

反応物 4

HCID 180AcetoneHCID 6363IsopropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86651813(1'-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methanamine tris(2,2,2-trifluoroacetate)

生成物 1

HCID 69811460N-((1'-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methyl)propan-2-amine収率 18%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

(1′-Benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methanamine tris(2,2,2-trifluoroacetate) (606 mg, 0.762 mmol) was stirred in a solution of acetone (0.280 mL, 3.81 mmol) and DCE (5 mL) for 15 minutes. NaBH(OAc)3 (323 mg, 1.52 mmol) was added in one portion and resulted in vigorous evolution of gas. After 1 hour at room temperature, LCMS suggested complete conversion to the desired isopropylamine. The reaction was concentrated and partitioned between EtOAc and 10% aqueous K2CO3. The organic was washed with brine, dried over Na2SO4 and concentrated to a crude residue. The racemic crude was purified by silica gel chromatography (gradient: 5-100% (80 DCM: 19 MeOH: 1 NH4OH)/DCM). Purification provided N-((1′-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine (68 mg, 0.137 mmol, 18.0% yield) as an oil. 1H NMR (CDCl3, 400 MHz) δ 8.62 (s, 1H), 7.27-7.33 (m, 5H), 7.24 (m, 1H), 7.18 (t, 1H), 6.96 (d, 1H), 3.95 (m, 4H), 3.54 (s, 2H), 3.27 (m, 1H), 2.84-2.99 (m, 5H), 2.63 (dt, 1H), 2.03-2.31 (m, 4H), 1.86 (m, 1H), 1.70 (dd, 2H), 1.42 (m, 2H), 1.15-1.119 (m, 7H), 0.78 (t, 3H). MS (APCI+) [M+H]: 496.3. Separation of isomers was conducted by preparative HPLC using a Chiralpak AD-H column (4.6×100 mm). The compound was eluted with 25% methanol/water (0.1% TEA additive) at 3 mL/min and 120 bars.

後処理

  1. customresulted in vigorous evolution of gas
  2. concentrationThe reaction was concentrated
  3. custompartitioned between EtOAc and 10% aqueous K2CO3
  4. washThe organic was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a crude residue
  7. customThe racemic crude was purified by silica gel chromatography (gradient: 5-100% (80 DCM: 19 MeOH: 1 NH4OH)/DCM)
  8. customPurification

出典と根拠

ORDレコード
ord-ed62a519a65e485f80d3798e0c9fdd89
出典データセット
uspto-grants-2016_05
特許番号
US09346805B2

反応ノート

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