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Dimethyl Sulfoxide → 4-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(((1R,3S)-3-hydroxycyclo-hexyl)amino)pyrimidine-5-carboxamide

HRID 2201986
ノート
印刷プレビュー

反応式

HRID 2201986 の反応式
[C:1]12([NH:6][C:7]3[C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=[C:9](Cl)[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.[NH2:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][C@H:20]([OH:24])[CH2:19]1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>CCOC(C)=O.C1COCC1.O>[C:1]12([NH:6][C:7]3[C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=[C:9]([NH:17][C@@H:18]4[CH2:23][CH2:22][CH2:21][C@H:20]([OH:24])[CH2:19]4)[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2
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

8

反応物 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 25630532(1S,3R)-3-aminocyclohexanolHCID 1182537854-(Bicyclo[1.1.1]pentan-1-ylamino)-2-chloropyrimidine-5-carboxamide

生成物 1

HCID 712372914-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(((1R,3S)-3-hydroxycyclo-hexyl)amino)pyrimidine-5-carboxamide収率 79%

試薬・触媒・溶媒 3

HCID 962Water溶媒
HCID 8028Tetrahydrofuran溶媒
HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

A mixture of 4-(bicyclo[1.1.1]pentan-1-ylamino)-2-chloropyrimidine-5-carboxamide (44 g), (1S,3R)-3-aminocyclohexanol (27.6 g), potassium carbonate (38.2 g) and DMSO (300 mL) was heated at 85° C. for 12 h. After cooling to room temperature, water (2 L) and a mixture of THF and EtOAc (1:1, 2 L) were added. The aqueous phase was separated and the organic layer was washed with saturated brine (2 L). The organic layer was concentrated under reduced pressure to give the crude product as a purple foam which was triturated with hot acetonitrile (1 L). After cooling to room temperature the solid was filtered and washed with acetonitrile (200 mL). The solids was dried in a vacuum oven at 50° C. to give 4-(bicyclo[1.1.1]pentan-1-ylamino)-2-(((1R,3S)-3-hydroxycyclohexyl)amino)pyrimidine-5-carboxamide as an off-white solid (4 g, 79% yield). 1H NMR (DMSO-d6) δ 0.91-1.31 (m, 4H), 1.60-1.89 (m, 3H), 2.01-2.20 (m, 7H), 3.34 (s, 1H), 3.37-3.52 (m, 1H), 3.58-3.85 (m, 1H), 4.65 (d, J=4.3 Hz, 1H), 6.90 (br. s., 1H), 7.20 (d, J=7.9 Hz, 1H), 7.61 (br. s., 1H), 8.37 (s, 1H), [9.23 (s, 0.14H)], 9.41 (s, 0.86H).

後処理

  1. temperatureAfter cooling to room temperature
  2. additionwere added
  3. customThe aqueous phase was separated
  4. washthe organic layer was washed with saturated brine (2 L)
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customto give the crude product as a purple foam which
  7. customwas triturated with hot acetonitrile (1 L)
  8. temperatureAfter cooling to room temperature the solid
  9. filtrationwas filtered
  10. washwashed with acetonitrile (200 mL)
  11. customThe solids was dried in a vacuum oven at 50° C.

出典と根拠

ORDレコード
ord-bca6934de3ff46bd93251da66bd344dc
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09365524B2

反応ノート

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