1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246656ノート

反応式

HRID 246656 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20](O)=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[NH2:23][C@@H:24]([CH3:27])[CH2:25][OH:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20]([NH:23][C@@H:24]([CH3:27])[CH2:25][OH:26])=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 80307L-AlaninolHCID 81531DiisopropylethylamineHCID 712803892-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

生成物 1

HCID 71279577(S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide収率 26%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (200 mg, 0.638 mmol), (S)-2-aminopropan-1-ol (57 mg, 0.765 mmol), EDCI (366 mg, 1.914 mmol), HOBt (258 mg, 1.914 mmol) and DIPEA (247 mg, 1.914 mmol) in dry DMF (10 mL) was stirred for 16 hours at room temperature. Water (10 mL) was added, the formed precipitate was separated by filtration, washed with methanol (1 mL) then was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.) to afford (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (46 mg, 26% for two steps) as a yellow solid. LCMS: (M+H)+=371; 1H NMR (300 MHz, DMSO+D2O): δ 9.14 (s, 1H), 8.59 (d, 1H, J=8.7 Hz), 8.36 (s, 1H), 7.72 (s, 1H), 7.27 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 4.23-4.18 (m, 1H), 3.55 (d, 1H, J=4.2 Hz), 1.25 (d, 1H, J=6.6 Hz).

後処理

  1. customthe formed precipitate was separated by filtration
  2. washwashed with methanol (1 mL)
  3. customthen was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  4. wait30% acetonitrile/70% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.

出典と根拠

ORDレコード
ord-32e11ff6be7a40b1ad31fcac9ea26c15
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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