ホームMCPワークベンチSkills
ホームワークベンチ通知マイページ
llms.txt · MCPガイドプライバシーポリシー · 利用規約 · サポートv1.8.0
  1. ホーム
  2. /反応

Phosphoric Acid → (3R)-3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile phosphate salt

HRID 334241
ノート
印刷プレビュー

反応式

HRID 334241 の反応式
[CH:1]1([C@H:4]([N:8]2[CH:12]=[C:11]([C:13]3[C:14]4[CH:21]=[CH:20][NH:19][C:15]=4[N:16]=[CH:17][N:18]=3)[CH:10]=[N:9]2)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1.[OH:22][P:23]([OH:26])([OH:25])=[O:24]>C(O)(C)C>[P:23]([OH:26])([OH:25])([OH:24])=[O:22].[CH:1]1([C@H:4]([N:8]2[CH:12]=[C:11]([C:13]3[C:14]4[CH:21]=[CH:20][NH:19][C:15]=4[N:16]=[CH:17][N:18]=3)[CH:10]=[N:9]2)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 1004Phosphoric AcidHCID 59420134(3R)-3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile

生成物 1

HCID 68472838(3R)-3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile phosphate salt収率 94.5%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒2 回

反応条件

温度
77 °C

実験手順

A suspension of (3R)-3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile ((R)-30, 60.0 g, 0.2158 mol, 1.0 equiv) in isopropanol (IPA, 900 mL) was heated to 77° C. to give a clear pale yellow solution. A solution of crystalline H3PO4 (23.3 g, 0.2374 mol, 1.1 equiv) in IPA (200 mL) was added in a steady stream from an addition funnel at 77-79° C., rinsing the addition funnel with IPA (25 mL). An immediate turbidity was developed followed by formation of a white suspension. After about half amount of the H3PO4 solution had been added the suspension became extremely thick. An additional amount of IPA (100 mL) was added to facilitate stirring. When addition was complete the suspension was heated at 75° C. for 1 h with the suspension becoming more mobile but remaining very thick. The suspension was cooled to room temperature over 1 h and the solids were collected by filtration and washed with 50% IPA/heptane (750 mL) and dried. The solids were triturated with heptane (1.2 L) with stirring for overnight before being collected by filtration and washed with heptane (300 mL) and dried in vacuum oven at 40-50° C. to constant weight to afford (3R)-3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile phosphate salt ((R)-31, Phosphate, 76.7 g, 81.2 g theoretical, 94.5% yield) as a fine white crystalline solid. For (R)-31: 1H NMR (DMSO-d6, 400 MHz) δ ppm 12.2 (bs, 1H), 9.62 (bs, 3H, H3PO4), 8.77 (s, 1H), 8.69 (s, 1H), 8.39 (s, 1H), 7.59 (q, 1H, J=2.0 Hz), 6.98 (d, 1H, J=2.7 Hz), 4.04 (m, 1H), 3.37 (dd, 1H, J=16.8, 8.0 Hz), 3.28 (dd, 1H, J=16.8, 5.1 Hz), 1.43 (m, 1H), 0.68 (m, 1H), 0.49 (m, 3H); 13C NMR (DMSO-d6, 100 MHz) δ ppm 152.2, 150.9, 149.9, 139.3, 130.4, 127.0, 120.8, 118.1, 112.9, 100.0, 62.6, 23.3, 15.7, 4.3, 3.8; C15H14N6 (MW, 278.31), LCMS (EI) m/e 279.1 (M++H).

後処理

  1. customto give a clear pale yellow solution
  2. washrinsing the addition funnel with IPA (25 mL)
  3. additionAfter about half amount of the H3PO4 solution had been added the suspension
  4. additionAn additional amount of IPA (100 mL) was added
  5. additionWhen addition
  6. temperaturewas heated at 75° C. for 1 h with the suspension
  7. temperatureThe suspension was cooled to room temperature over 1 h
  8. filtrationthe solids were collected by filtration
  9. washwashed with 50% IPA/heptane (750 mL)
  10. customdried
  11. customThe solids were triturated with heptane (1.2 L)
  12. stirringwith stirring for overnight
  13. filtrationbefore being collected by filtration
  14. washwashed with heptane (300 mL)
  15. customdried in vacuum oven at 40-50° C. to constant weight

出典と根拠

ORDレコード
ord-441fd0404cbd4d5491eb786b7d01d8ed
出典データセット
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08883806B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート