Hydrochloric Acid → 5-Fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamine

HRID 705560Notes

Reaction equation

HRID 705560 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([F:9])=[CH:4][N:3]=1.[S:10]1[CH:14]=[CH:13][CH:12]=[C:11]1[CH2:15][OH:16].CC([O-])(C)C.[K+].Cl>>[F:9][C:5]1[C:6]([NH2:8])=[N:7][C:2]([O:16][CH2:15][C:11]2[S:10][CH:14]=[CH:13][CH:12]=2)=[N:3][CH:4]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 694672-ThiophenemethanolHCID 2543722-Chloro-5-fluoropyrimidin-4-amineHCID 23665647Potassium tert-butoxide

Product 1

HCID 578186595-Fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamineYield 137.1%

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-chloro-5-fluoropyrimidin-4-ylamine (2.00 g, 13.5 mmol) and thiophen-2-ylmethanol (1.92 g, 16.9 mmol) with a magnetic stir bar in a 20 mL Biotage Initiator microwave reaction vessel was added KOtBu (17.0 mL of 1M in tBuOH, 17.0 mmol). The resulting mixture was sealed with a Biotage Initiator microwave septa cap and heated in a Biotage Initiator microwave to 100° C. for 30 min. The heating cycle was repeated (2×) for a total reaction time of 90 min. The contents were poured into ice-water and the pH was adjusted to neutral with 2N HCl. The resulting solid was filtered and washed with water (2×) and then 20% ether/hexanes (100 mL). The remaining solid was dried overnight at 50° C. under vacuum to give 4.17 g (68%) of 5-fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamine as a pale yellow powder: mp 92-94° C.; 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J=2.7 Hz, 1H), 7.29 (m, 1H), 7.13 (d, J=3.6 Hz, 1H), 6.97 (m, 1H), 5.46 (s, 2H), 5.17 (br s, 2H); MS (ESI) m/z 226 (M+H)+.

Workup

  1. customin a 20 mL Biotage Initiator microwave reaction vessel
  2. customThe resulting mixture was sealed with a Biotage Initiator microwave
  3. customsepta cap
  4. customfor a total reaction time of 90 min
  5. filtrationThe resulting solid was filtered
  6. washwashed with water (2×)
  7. customThe remaining solid was dried overnight at 50° C. under vacuum

Sources & evidence

ORD record
ord-d8bcb5457e0b44f4af700dd53d786085
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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