Sodium Hydroxide → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acid

HRID 1410014ノート

反応式

HRID 1410014 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[C:28]([OH:36])[CH:27]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[C:28]([OH:36])[CH:27]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 68379322Methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate

生成物 1

HCID 665515464-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acid収率 14%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoate in 5 mL of THF and 5 mL of methanol was added a solution of 1N NaOH (5 mL) at room temperature. After the addition, the reaction was stirred at this temperature for 16 hours. The solvent was evaporated and the residue was diluted with water and adjusted to pH=2 by HCl (aq.). The suspension was filtered and dried. The crude 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: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)-2-hydroxybenzoic acid (15 mg, 14% over two steps). 1H NMR (300 MHz, DMSO): δ 9.72 (s, 1H), 8.85 (s, 1H), 8.76 (d, 1H, J=6.0 Hz), 7.86 (s, 1H), 7.84 (s, 1H), 7.43-7.37 (m, 3H), 6.92 (d, 1H, J=8.4 Hz), 4.56 (brs, 1H), 3.77-3.73 (m, 11H), 2.27-2.23 (m, 1H), 2.09-2.07 (m, 1H). LC-MS: 537 [M+H]+, tR=1.37 min. HPLC: 99.62% at 214 nm, 99.22% at 254 nm, tR=3.53 min.

後処理

  1. additionAfter the addition
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water
  4. filtrationThe suspension was filtered
  5. customdried
  6. customThe crude was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  7. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.

出典と根拠

ORDレコード
ord-0a372c8c84dd4903814dc4350e6c8090
出典データセット
uspto-grants-2014_12
特許番号
US08921383B2

反応ノート

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