Hydrochloric Acid → (2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamide

HRID 1098042ノート

反応式

HRID 1098042 の反応式
Cl.[Si]([O:19][CH2:20][CH2:21][O:22][CH2:23][C@H:24]([O:35][C:36]1[C:37]2[N:44]=[N:43][N:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[Cl:51])[C:38]=2[N:39]=[CH:40][N:41]=1)[C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=1)=[O:26])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CO>[Cl:51][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=1[N:42]1[C:38]2[N:39]=[CH:40][N:41]=[C:36]([O:35][C@@H:24]([CH2:23][O:22][CH2:21][CH2:20][OH:19])[C:25]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=3)=[O:26])[C:37]=2[N:44]=[N:43]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 57504543(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)propanamide

生成物 1

HCID 57504544(2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamide収率 31.4%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Hydrochloric acid (10%, 1 mL) was added dropwise to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)propanamide (Intermediate AP4) (180 mg, 0.25 mmol) in methanol (20.00 mL) at room temperature. The resulting solution was stirred for 4 hours. Most of the methanol was evaporated and the remaining aq. soln was diluted with saturated NH4Cl and extracted with EtOAc (2×30 mL). The organic layers were combined, dried (MgSO4) and evaporated to give crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)propanamide (38.0 mg, 31.4%). 1H NMR (400 MHz, CDCl3) δ3.72-3.83 (m, 4H), 4.19-4.32 (m, 2H), 6.15 (t, 1H), 7.50-7.63 (m, 3H), 7.66-7.72 (m, 2H), 8.15-8.27 (m, 2H), 8.72 (s, 1H), 9.16 (s, 1H) OH not observed; m/z (ESI+) (M+H)+=490.16; HPLC tR=2.15 min

後処理

  1. customMost of the methanol was evaporated
  2. additionthe remaining aq. soln was diluted with saturated NH4Cl
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give crude product
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-46071383d5b043aa88ac12a7224ecf83
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

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