Sodium borohydride → Methyl (2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

HRID 1400743ノート

反応式

HRID 1400743 の反応式
[CH2:1]([O:4][C:5]1([CH3:50])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=5[O:33][C@H:34]([CH2:36][CH:37]=[CH2:38])[CH3:35])[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:39])[C:12]=2[C@H:40]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[C:41]([O:43][CH3:44])=[O:42])[CH2:7][CH2:6]1)C=C.[BH4-].[Na+]>ClCCCl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.CCOC(C)=O>[C:46]([O:45][C@@H:40]([C:12]1[C:13]([CH3:39])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:7][CH2:6][C:5]([CH3:50])([O:4][CH2:1][CH2:38][CH2:37][CH2:36][C@H:34]([CH3:35])[O:33][C:27]2[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:26]=2[C:22]2[CH:21]=[C:20]3[CH:25]=[CH:24][CH:23]=2)[CH2:10][CH2:9]1)[C:41]([O:43][CH3:44])=[O:42])([CH3:48])([CH3:47])[CH3:49]

参加物

6

反応物 2

HCID 4311764Sodium borohydrideHCID 86710799(S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5'-fluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

生成物 1

HCID 86710798Methyl (2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

試薬・触媒・溶媒 3

HCID 178425456HCID 178425456、化合物触媒HCID 111,2-Dichloroethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of (S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5′-fluoro-2′-((S)-pent-4-en-2-yloxy)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.17 g, 0.25 mmol, 1 equiv) in DCE (50 mL) was heated to 80° C. The Hoyveda Grubbs 2nd generation catalyst (31 mg, 0.05 mmol, 0.2 equiv) was added. The pale green brown solution was stirred for 1.5 h and then allowed to cool to ambient temperature. The reaction was concentrated in vacuo. The dark residue was then taken up in MeOH (5 mL) and NaBH4 (13 mg, 0.35 mmol, 1.4 equiv) was added. After stirring 30 min, the reaction was diluted with EtOAc and washed with water. The EtOAc layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc in hexane) to provide the product as a colorless film (62 mg, 38%). 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.80 (s, 1H), 7.51 (s, 1H), 7.39-7.31 (m, 1H), 7.09 (s, 1H), 7.05-6.87 (m, 3H), 5.93-5.82 (m, 1H), 4.68-4.42 (m, 2H), 4.27-4.17 (m, 1H), 3.84-3.68 (m, J=3.5 Hz, 4H), 3.56-3.22 (m, 2H), 3.03-2.85 (m, 1H), 2.62 (br. s., 3H), 2.02-1.70 (m, J=12.8 Hz, 10H), 1.26-1.21 (m, 12H), 1.15 (d, J=6.0 Hz, 3H). LCMS (M+1)=659.45.

後処理

  1. concentrationThe reaction was concentrated in vacuo
  2. stirringAfter stirring 30 min
  3. washwashed with water
  4. dry with materialThe EtOAc layer was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (0-100% EtOAc in hexane)
  7. customto provide the product as a colorless film (62 mg, 38%)

出典と根拠

ORDレコード
ord-b277454634ce4e1b8ffed4bd81b9eba7
出典データセット
uspto-grants-2014_12
特許番号
US08906929B2

反応ノート

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